Longitudinal assessment of premorbid cognitive functioning in patients with schizophrenia through examination of standardized scholastic test performance

OBJECTIVE: Studies suggest the presence of premorbid cognitive impairment in patients with schizophrenia, yet the onset and course of these deficits remain unclear. The purpose of this study was to investigate the longitudinal course of premorbid cognitive functioning in individuals with schizophrenia by using prospective data obtained from scholastic test results. METHOD: Scores from grades 4, 8, and 11 on the Iowa Tests of Basic Skills and the Iowa Tests of Educational Development were obtained for 70 subjects who later developed schizophrenia. The mean percentile rank of the subjects' scores in the areas of vocabulary, reading comprehension, language, mathematics, sources of information, and an overall composite category were compared with state norms. RESULTS: The subjects scored below the 50th percentile for each category in all three grades, but only language, reading, sources of information, and composite scores from grade 11 were significantly below state norms. With regard to longitudinal course, there was a significant linear decrease in language scores over time. Scores from grade 11 were positively correlated with WAIS-R IQ, verbal fluency, and Rey Auditory Verbal Learning scores at first illness episode. Scores from grade 11 were not significantly correlated with age at illness onset or ratings of disorganized, psychotic, or negative symptoms. CONCLUSIONS: Scholastic test scores at grades 4 and 8 were nonsignificantly below average in this group of children who later developed schizophrenia. However, test scores dropped significantly between grades 8 and 11. This corresponds to ages 13-16 years, or the onset of puberty. Poor or declining scholastic performance may be a precursor to the cognitive impairment seen during the first episode of illness.     

A retrospective study of premorbid ability and aging differences in cognitive clusters of schizophrenia

This retrospective, cross-sectional study evaluated whether age-related differences in patterns of cognitive deficit exist among four cognitively based schizophrenia subgroups. These subgroups had previously been identified through cluster analyses of a battery of abstraction and problem-solving tests in large samples. Evaluation of estimated premorbid intellectual ability and postmorbid cognitive functioning stratified by decade from the twenties through the fifties revealed different patterns across the schizophrenia subgroups and a clinical comparison sample. A near normal cognitive subgroup demonstrated relatively high premorbid intellectual ability and a pattern of age differences similar to the comparison sample, with the exception of deficits on the Wisconsin Card Sorting Test that were detectable in the twenties and remained stable thereafter. In contrast, a subgroup characterized by severe, pervasive cognitive deficit demonstrated low premorbid intellectual ability and extremely low test scores across the four decades studied. The remaining clusters were characterized by moderate cognitive impairment and showed age differences suggestive of a decline in cognitive function around the time of illness onset that remained stable. Results provide further support for the validity of these subgroups and encourage continued efforts to identify cognitively based candidate schizophrenia subtypes.     

Impairment in test performance and symptom dimensions of schizophrenia

Schizophrenic patients were rated on three syndromal dimensions derived from positive and negative symptom ratings. Scores on each dimension were compared to performance on neuropsychological tests before and after coaching instructions. Patients evidenced significant improvement in performance on all measures readministered immediately after instruction. Disorganization symptoms were correlated with lower levels of performance on all pre-coaching, trial 1 tests. Disorganization symptoms were also associated with lower levels of trial 2 post-coaching performance, independent of pre-coaching scores. These results suggest that, within a population of schizophrenic patients, symptoms of disorganization are associated with relatively greater impairments in performance on neuropsychological tests and with impaired ability to improve test performance following coaching instructions. The three symptom dimensions show promise for reducing heterogeneity within samples of schizophrenic patients.     

精神分裂症患者认知损害的临床常用测查方法

精神分裂症合并有认知功能损害的观点,已成为多数医生的共识[1]。但是,针对精神分裂症认知损害的测查方法却不尽统一,方法和综述类文章较多。有关认知功能的测查,总体上分为两大类,一是个体认知功能测查,包括个体的认识、理解、处理事物的能力,涉及感觉、知觉、定向、记忆、计算、理解、分析和判断能力等;二是社会认知功能,包括情绪认知、心理理论和归     

Family-based association study of SELENBP1 in schizophrenia

The SELENBP1 gene previously was found to be up-regulated in microarray analysis of both peripheral blood cell and brain tissue samples from schizophrenia patients. Quantitative PCR analysis subsequently corroborated the altered expression of SELENBP1 in schizophrenia brain tissue samples from the Stanley Array Correction. The aim of this study was to extend those findings by employing family-based association methods to a sample of over 2400 individuals (including 1214 individuals affected by schizophrenia) of Han Chinese descent living in Taiwan. One of four haplotype-tagging SNPs and two different two-marker haplotypes showed nominally significant evidence for association with schizophrenia under an additive model, suggesting that genetic variation in SELENBP1 may influence risk for the disorder, while this significance did not remain when other inheritance models were considered. Further comprehensive analysis with other SNPs and haplotypes is needed and warranted.     

Impact of cognitive performance on the reproducibility of fMRI activation in schizophrenia

Background

Longitudinal functional magnetic resonance imaging (fMRI) studies in patients with schizophrenia allow exploration of the course of the illness and brain activity after therapy. A crucial question, however, is whether fMRI findings are reliable, because they can be affected by performance deficits in patients with schizophrenia. Our aim was to evaluate the reproducibility of fMRI activations in highly integrated language areas in patients with schizophrenia, taking into account task performance.

Methods

Ten patients with schizophrenia and 10 matched healthy controls were scanned twice, 21 months apart, while performing a story comprehension task. The reproducibility of the activations in each participant was evaluated globally by the percentage of spatial overlap between the 2 sessions and locally by a voxel-wise computation of the between-session relative standard deviation. We performed between-group comparisons both with and without the inclusion of comprehension scores (measuring task performance) as a covariate.

Results

On average, patients with schizophrenia had significantly lower comprehension scores than controls (4.5/12 v. 7.8/12, p = 0.002). The mean spatial overlap between fMRI sessions was 30.6% in the patient group and 47.0% in the control group (p = 0.017). Locally, the lower reproducibility in patients was most prominent in the left posterior middle temporal gyrus, inferior frontal gyrus and medial prefrontal cortex (p < 0.001 uncorrected for multiple comparisons). Comprehension scores were positively correlated with both reproducibility measures in patients (overlap: r = 0.82, p = 0.004; relative standard deviation: several significant clusters at p < 0.001). When we included the comprehension scores as a covariate, most of the local between-group differences in reproducibility were removed, and the difference in overlap was not significant.

Limitations

Owing to the small sample size, we could not investigate the impact of clinical subtypes and different types of medications on reproducibility.

Conclusion

Our findings suggest that the greater variability in activation in patients with schizophrenia compared with controls concerns high-level areas and is mainly attributable to deficient task performance. Consequently, cognitive performance must be carefully controlled when longitudinal fMRI studies are undertaken.     

Relationship of affect recognition with psychopathology and cognitive performance in schizophrenia.

The purpose of the present study was to explore the relationship between emotion perception and both psychopathology and cognitive functioning in a group of Greek patients with schizophrenia. Thirty-five patients with schizophrenia were assessed with computerized tests of emotion perception, using visual faces (Kinney's Affect Matching Test, KAMT), prosody (Affective Prosody Test, APT), and visual everyday scenarios (Fantie's Cartoon Test, FCT), as well as a facial recognition test (Kinney's Identity Matching Test, KIMT). The patients were also evaluated with the symptoms dimensions derived from the PANSS (positive, negative, cognitive, depression, and excitement) and a battery of neuropsychological tests measuring executive functions, attention, working memory, verbal and visual memory, visuospatial ability, and visual scanning/psychomotor speed. The three emotion perception and face recognition tests correlated significantly with each other. The KAMT was significantly related to the cognitive symptoms dimension of the PANSS and executive functions. The FCT was significantly related to level of education and attention. Finally, the APT was significantly related to the cognitive symptoms dimension, executive functions, and attention. Our findings regarding the significant relationships of affect perception, both facial and vocal, as well as in everyday scenarios, with several cognitive abilities support the notion that deficits in decoding affective information in schizophrenia could be attributed to impairment in more basic neurocognitive domains.     

Family-based association studies of CAPON and schizophrenia in the Chinese Han population

Although there is evidence pointing to CAPON as a susceptible gene for schizophrenia, the results of independent association studies have so far been inconsistent. A recent case-control study by Zheng et al. supported CAPON as a susceptible site for the disease in the Chinese Han population. In their study both the single polymorphism (rs348624) and individual haplotypes showed significant association with schizophrenia. Our study further investigates this relationship this time using a family-based association. We selected 5 SNPs including rs348624 and performed a Transmission Disequilibrium Test (TDT) in 319 Chinese Han trios. Our results identified no single marker nor haplotype associated with schizophrenia, which did not suggest that CAPON was a susceptible site in the Chinese Han population, or it appeared unlikely that the CAPON played a major role in the aetiology of schizophrenia. Since there is consistent evidence pointing to 1q21-22 as a positional candidate region for schizophrenia, we suggest that further research should focus on other genes located in this region.     

Predictors of performance improvements within a cognitive remediation program for schizophrenia

Cognitive impairment is regarded a core feature of schizophrenia and is associated with low psychosocial functioning. There is rich evidence that cognitive remediation can improve cognitive functions in patients with schizophrenia. However, little is known about what predicts individual remediation success. Some studies suggest that baseline cognitive impairment might be a limiting factor for training response. Aim of the current study was to further examine the role of cognitive and symptom variables as predictors of remediation success. We studied a total sample of 32 patients with schizophrenia and schizoaffective disorder who were engaged in a computer-based cognitive training program (CogPack). A pre-training test battery provided cognitive measures of selective attention, executive functioning, processing speed, verbal memory, and verbal intelligence along with measures for positive and negative symptoms. Training response was defined as improvement on training tasks. Correlation analyses revealed no significant relationship between any of the baseline cognitive or symptom measures and improvement rates. However, better baseline cognition was associated with a higher percentage of tasks with initial ceiling effects. We conclude that not carefully tailoring task difficulty to patients' cognitive abilities constitutes a much more severe threat to cognitive remediation success than cognitive impairment itself.     

Initial and final work performance in schizophrenia: cognitive and symptom predictors

Studies have shown that cognitive functioning may limit the rate, tenure, and type of work performed by people with schizophrenia. The present study tested the hypothesis that cognitive abilities needed for initial improvement in work performance would differ from those needed in later vocational development. Ninety-six outpatients with schizophrenia or schizoaffective disorder who participated in a work rehabilitation program were administered neuropsychological testing at intake. Their work performance was evaluated biweekly for 26 weeks. Cognitive test variables were entered into regressions predicting the slope of individual performance curves from weeks 1 to 13 and 13 to 26. Neuropsychological variables accounted for 28% of the variance in slope during the initial period. The strongest predictor was a Continuous Performance Task variable that measures inattentiveness. Other important variables were measures of idiosyncratic thinking, cognitive flexibility, and verbal memory. Neuropsychological variables accounted for 19% of the variance in the slope during the final period. The strongest predictor was verbal learning, while measures of cognitive impulsivity and psychomotor functioning were also significant contributors. There was no relationship between work performance and symptoms for weeks 1 to 13 or 13 to 26. These findings suggest that while attention is more important for initial success, verbal memory becomes more important for sustained improvement. Remediating or accommodating such deficits in a time-sensitive fashion may be a necessary feature for successful rehabilitation.     

Habenula lesions cause impaired cognitive performance in rats: implications for schizophrenia

Cognitive impairment is a prominent feature of schizophrenia. Currently there is no well-accepted explanation of the aetiology of this disorder, but recent evidence indicates that dysfunction of the habenula may be involved. We therefore examined whether habenula lesions in Sprague-Dawley rats cause behavioural changes resembling those of schizophrenia. Rats received either habenula lesions, a sham operation or a small lesion of the overlying dorsal hippocampus as a check that effects observed were not due to incidental damage to this structure. As there are alterations of social behaviour, sensorimotor gating and cognition in schizophrenia, we examined comparable behaviours. Social interaction time was measured during a 5-min encounter with a novel juvenile conspecific. Prepulse inhibition of an acoustic startle response, as an index of sensorimotor gating, was measured with prepulses of various amplitudes, and spatial cognitive performance was assessed in the Morris water maze task. Histological analysis showed that habenula lesions substantially damaged both medial and lateral habenula bilaterally while largely sparing neighbouring structures. Assay of choline acetyltransferase (ChAT) in the interpeduncular nucleus terminal region of the habenulo-interpeduncular tract, showed marked reduction (by 80%) in habenula-lesioned animals. Habenula-lesioned rats, but not the control group with small dorsal hippocampus lesions, showed marked impairment of Morris maze performance compared to the sham-operated control group. Social interaction time and prepulse inhibition were not significantly altered in either lesion group. The results are consistent with a role of the habenula in cognition, and with the view that pathology of the habenula may contribute to the cognitive impairments of schizophrenia.     

Ventricular size, cognitive and psychomotor performance, and laterality in schizophrenia

Based on the association of cerebral ventricular enlargement with cognitive impairments in schizophrenia, the present study looked for relationships between the hemispheric ventricular size and tests of performance as well as their sensitivity to neuroleptics. No meaningful relations could be established. On the contrary, wider ventricles were associated with less cognitive and psychomotor impairment and less sensitivity to neuroleptics.     

Enhancement of cognitive performance in schizophrenia by addition of tandospirone to neuroleptic treatment

OBJECTIVE: The goal of this study was to evaluate the effects of the addition of tandospirone, a serotonin-1A (5-HT(1A)) agonist, to ongoing treatment with typical antipsychotic drugs, on two cognitive domains that are relevant to functional outcome in patients with schizophrenia. METHOD: Twenty-six patients with schizophrenia who were receiving stable doses of typical antipsychotics were randomly assigned to adjunctive treatment with 30 mg/day of tandospirone or placebo for 6 weeks. Executive function and verbal memory as well as psychopathology were assessed at baseline and after 6 weeks. RESULTS: Both cognitive measures improved significantly in the patients who received tandospirone; subjects who did not receive tandospirone showed no change. There was no significant change in psychopathology ratings in either group. CONCLUSIONS: The results suggest the usefulness of 5-HT(1A) agonists for enhancing some types of cognitive performance and possibly social and work function in patients with schizophrenia.