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Previous work suggests that impairments in executive function and verbal memory in particular may persist in euthymic bipolar patients and serve as an indicator of genetic risk (endophenotype).
A systematic review of the literature was undertaken. Effects sizes were extracted from selected papers and pooled using meta-analytical techniques.
In bipolar patients, large effect sizes (d>0.8) were noted for executive functions (working memory, executive control, fluency) and verbal memory. Medium effect sizes (0.5<d<0.8) were reported for aspects of executive function (concept shifting, executive control), mental speed, visual memory, and sustained attention. Small effect sizes (d<0.5) were found for visuoperception. In first-degree relatives, effect sizes were small (d<0.5), but significantly different from healthy controls for executive function and verbal memory in particular.
Executive function and verbal memory are candidate bipolar endophenotypes given large deficits in these domains in bipolar patients and small, but intermediate, cognitive impairments in first-degree relatives.
Deficits in theory of mind (ToM), or the ability to infer what another person is thinking or feeling, have been reported in manic and euthymic adults with bipolar disorder. To date, there have been no investigations of ToM in pediatric bipolar disorder (PBD). The aim of the current study was to investigate this ability in PBD patients and healthy controls.
PBD patients (n=26) and intellectually and demographically similar healthy comparison subjects (n=20) were administered two ToM tasks. In the Affective Story Task, subjects were read positive-, negative- and neutral-valenced stories, and were assessed on their ability to recognize that a misleading series of events could lead one character to develop a false belief about another character. On the Hinting Task, subjects were required to infer the real intentions behind subtle hints.
The PBD group performed significantly more poorly than controls on the Hinting Task and the positive and negative conditions of the Affective Story Task. In the PBD group only, younger age, earlier illness onset and manic symptoms were associated with poorer ToM performance.
Consistent with past findings in adult bipolar disorder (BD), PBD youth performed more poorly than controls on ToM tasks. Data suggest that ToM ability may be more impaired in affectively charged contexts. Additionally, an earlier onset of illness among PBD youth may interfere with the development of social-cognitive skills. ToM disturbances may be a useful treatment target in PBD, with the aim of facilitating more accurate assessment of social cues and better interpersonal functioning.
The ability to appreciate humour is essential to successful human interactions. In this study, we hypothesized that individuals with schizophrenia would have diminished ability to recognize and appreciate humour. The relationship between humour experience and clinical symptoms, cognitive and social functioning was examined.
Thirty patients with a DSM-IV diagnosis of schizophrenia were compared with 30 age-, gender-, IQ- and ethnicity-matched healthy controls. Humour recognition was measured by identification of humorous moments in four silent slapstick comedy film clips and calculated as d-prime (d′) according to signal detection theory. Humour appreciation was measured by self-report mood state and funniness ratings. Patients were assessed for clinical symptoms, theory of mind ability, executive function [using the Wisconsin Card Sorting Test (WCST)] and social functioning [using the Life Skills Profile (LSP)].
Patient and control groups did not differ in the funniness ratings they attributed to the video clips. Patients with schizophrenia had a lower d′ (humour) compared to the controls, after controlling for (1) the performance of a baseline recognition task with a non-humorous video clip and (2) severity of depressive symptoms. In patients, d′ (humour) had significant negative correlation with delusion and depression scores, the perseverative error score of the WCST and the total scores of the LSP.
Compared with controls, patients with schizophrenia were less sensitive at detecting humour but similarly able to appreciate humour. The degree of humour recognition difficulty may be associated with the extent of executive dysfunction and thus contribute to the psychosocial impairment in patients with schizophrenia.
Source monitoring consists in identifying the origin of mental events. Recent research suggests that confusions over internally generated mental events may represent a cognitive marker for increased proneness to psychotic symptoms and disorders. We have examined source monitoring for actions in adolescents with the 22q11.2 deletion syndrome (22q11DS), a neurogenetic disease associated with high rates of schizophrenia during adulthood, and expected to observe source monitoring deficits in comparison to IQ-matched and typically developing controls.
Eighteen adolescents with 22q11DS, 17 adolescents matched for age and IQ, and also 17 adolescents matched for age participated in this study. Our adapted action monitoring paradigm asked subjects to visualize a series of actions in three different conditions: (1) visualize themselves performing the action; (2) visualize the experimenter performing the action; or (3) simply repeat the action statements without visualization of the action performer.
The adolescents with 22q11DS performed adequately in terms of recognition (hits), but in comparison to both control groups, they committed more source confusions on correctly recognized items. Further examination revealed that the adolescents were more likely to demonstrate confusions between exterior sources in which the self was not involved.
Source monitoring deficits can be observed in adolescents with 22q11DS, a syndrome putting them at high risk for developing schizophrenia. These deficits are discussed in terms of early cognitive processes associated with genetic risk for schizophrenia.
Schizophrenic patients tend to attribute internal events to external agents, a bias that may be linked to positive symptoms. We investigated the effect of emotional valence on the cognitive bias.
Male schizophrenic subjects (n=30) and an experimenter alternatively produced neutral and negative words. The subject then decided whether he or the experimenter had generated the item.
External misattributions were more common than self-misattributions, and the bias was greater for patients with active hallucinations and delusions relative to patients in remission. Actively psychotic patients but not patients in remission were more likely to generate external misattributions with negative relative to neutral words.
Affective modulation of the externalizing cognitive bias in source monitoring is evident in patients with hallucinations and delusions.
In previous studies we suggested that liberal acceptance (LA) represents a fundamental cognitive bias in schizophrenia and may explain why patients are more willing to accept weak response alternatives and display overconfidence in incorrect responses. The aim of the present study was to test a central assumption of the LA account: false alarms in schizophrenia should be particularly increased when the distractor–target resemblance is weak relative to a control group.
Sixty-eight schizophrenia patients were compared to 25 healthy controls on a visual memory task. At encoding, participants studied eight complex displays, each consisting of a unique pairing of four stimulus attributes: symbol, shape, position and colour. At recognition, studied items were presented along with distractors that resembled the targets to varying degrees (i.e. the match between distractors and targets ranged from one to three attributes). Participants were required to make old/new judgements graded for confidence.
The hypotheses were confirmed: false recognition was increased for patients compared to controls for weakly and moderately related distractors only, whereas strong lure items induced similar levels of false recognition for both groups. In accordance with prior research, patients displayed a significantly reduced confidence gap and enhanced knowledge corruption compared to controls. Finally, higher neuroleptic dosage was related to a decreased number of high-confident ratings.
These data assert that LA is a core mechanism contributing to both enhanced acceptance of weakly supported response alternatives and metamemory deficits, and this may be linked to the emergence of positive symptomatology.
Although poor neuropsychological test performance is well documented in schizophrenia, how closely it resembles that seen in patients with brain damage in terms of cognitive failures in daily life and stability over time has been little studied.
Thirty patients with chronic schizophrenia, 24 patients with frontal or temporal brain damage and 30 healthy controls were given a battery of memory and executive tests. Carers of the two patient groups also completed questionnaires rating memory and executive failures in daily life. Testing was repeated 6 weeks later.
The schizophrenia and the brain-damaged patients were significantly impaired on most, but not all tests. The degree of carer-rated memory or executive failure was similar in the two groups, but the schizophrenia patients were rated as having significantly more executive failures than memory failures, whereas the brain-damaged patients showed the reverse pattern. Both groups of patients showed similar consistency of performance across sessions.
Neuropsychological impairment in schizophrenia resembles that seen in patients with brain damage, not only in terms of overall severity, but also in terms of stability and the degree to which poor test performance translates into cognitive failures in daily life.
Verbal learning and memory deficits are frequent among patients with schizophrenia and correlate with reduced magnetic resonance imaging (MRI) volumes of the hippocampus in these patients. A crucial question is the extent to which interrelated structural-functional deficits of the hippocampus reflect a vulnerability to schizophrenia, as opposed to the disorder per se.
We combined brain structural measures and the Rey Auditory Verbal Learning Test (RAVLT) to assess hippocampal structure and function in 36 never-medicated individuals suspected to be in early (EPS) or late prodromal states (LPS) of schizophrenia relative to 30 healthy controls.
Group comparisons revealed bilaterally reduced MRI hippocampal volumes in both EPS and LPS subjects. In LPS subjects but not in EPS subjects, these reductions were correlated with poorer performance in RAVLT delayed recall.
Our findings suggest progressive and interrelated structural-functional pathology of the hippocampus, as prodromal symptoms and behaviours accumulate, and the level of risk for psychosis increases. Given the inverse correlation of learning and memory deficits with social and vocational functioning in established schizophrenia, our findings substantiate the rationale for developing preventive treatment strategies that maintain cognitive capacities in the at-risk mental state.
Relationships between performance on various tests of executive functions and
positive symptoms, especially delusions and hallucinations, have not been
found consistently. This may be related to method of rating symptoms, to
possible interactions between them, as well as to the low specificity of the
cognitive test measures used. In this study, we have investigated the
relationships between different aspects of positive symptomatology and
several executive subprocesses.
Stable schizophrenia patients (n=96) were assessed for disorganization,
delusion and hallucination symptoms rated from the Scale for Assessment of
Positive Symptoms and the Scale for Assessment of Negative Symptoms.
Interference sensitivity, inhibition and flexibility were assessed using the
Wickens paradigm. The relationships between symptom dimensions as well as
with cognitive and other potentially confounding variables were assessed
using Pearson correlations and (simple and partial)
Generally consistent with the cognitive constructs used to account for
positive symptoms, the results indicated relationships between delusions,
disorganization and inhibition, and between hallucinations and interference
sensitivity. However, these relationships appeared more complex than
expected, with some being dependent on interactions between symptoms.
These results suggest: (i) that the global
measures usually employed may not be appropriate for demonstrating specific
relationships between symptoms and executive functions and
(ii) that it is necessary to take into account the
interactions between positive symptoms as well as with other factors to
reveal these relationships.
Ocular-motor inhibition errors and saccadic hypometria occur at elevated rates in biological relatives of schizophrenic patients. The memory-guided saccade (MS) paradigm requires a subject to inhibit reflexive saccades (RSs) and to programme a delayed saccade towards a remembered target.
MS, RS, and central fixation (CF) tasks were administered to 16 patients who met the criteria for DSM-IV schizophrenia, 19 of their psychiatrically healthy siblings, and 18 controls.
Patients and siblings showed elevated MS error rates reflecting a failure to inhibit RSs to a visible target, as required by the task. In contrast to controls, prior errors did not improve MS accuracy in patients and siblings.
The specific characteristics of the elevated MS error rate help to clarify the nature of the disinhibition impairment found in schizophrenics and their healthy siblings. Failure to inhibit premature saccades and to improve the accuracy of subsequent volitional saccades implicates a deficit in spatial working-memory integration, mental representation and/or motor learning processes in schizophrenia.
Results of studies on antisaccade (AS) deficit in relatives of patients with schizophrenia are inconclusive. We hypothesized that AS performance in siblings of patients with schizophrenia is worse than in healthy controls and better than in patients with schizophrenia.
We included 55 first-episode patients with schizophrenia, 28 healthy siblings and 36 healthy controls to evaluate AS performance. Eye movements were measured electromagnetically by the double magnetic induction (DMI) method.
Patients with schizophrenia had a significantly higher error rate than siblings (d=0.86, p<0.0001) and controls (d=1.35, p<0.0001). Siblings had a higher mean error rate than healthy controls but this did not reach significance (d=0.56, p=0.29). The intra-class correlation (ICC) was 0.33 for the error rate. Mean AS gain was higher in siblings than in patients (d=0.75, p=0.004) and controls (d=0.6, p=0.05). The ICC was 0.08.
AS parameters in strictly screened healthy young siblings of young first-episode patients with schizophrenia are comparable to results found in studies investigating older relatives. However, the statistical results (i.e. the ICCs) suggest that there is little evidence of shared environmental or genetic factors on error rate variation.
Diffusion tensor imaging (DTI) can be used to investigate cerebral structural connectivity in never-medicated individuals with first-episode schizophrenia.
Subjects with first-episode schizophrenia according to DSM-IV-R who had never been exposed to antipsychotic medication (n=25) and healthy controls (n=26) were recruited. Groups were matched for age, gender, best parental socio-economic status and ethnicity. All subjects underwent DTI and structural magnetic resonance imaging (MRI) scans. Voxel-based analysis was performed to investigate brain regions where fractional anisotropy (FA) values differed significantly between groups. A confirmatory region-of-interest (ROI) analysis of FA scores was performed in which regions were placed blind to group membership.
In patients, FA values significantly lower than those in healthy controls were located in the left fronto-occipital fasciculus, left inferior longitudinal fasciculus, white matter adjacent to right precuneus, splenium of corpus callosum, right posterior limb of internal capsule, white matter adjacent to right substantia nigra, and left cerebral peduncle. ROI analysis of the corpus callosum confirmed that the patient group had significantly lower mean FA values than the controls in the splenium but not in the genu. The intra-class correlation coefficient (ICC) for independent ROI measurements was 0.90 (genu) and 0.90 (splenium). There were no regions where FA values were significantly higher in the patients than in the healthy controls.
Widespread structural dysconnectivity, including the subcortical region, is already present in neuroleptic-naive patients in their first episode of illness.
Female patients with schizophrenia are less impaired in social life than male patients. Because social impairment in schizophrenia has been found to be associated with deficits in emotion recognition, we examined whether the female advantage in processing emotional prosody and semantics is preserved in schizophrenia.
Forty-eight patients (25 males, 23 females) and 46 controls (23 males, 23 females) were assessed using an emotional language task (in which healthy women generally outperform healthy men), consisting of 96 sentences in four conditions: (1) neutral-content/emotional-tone (happy, sad, angry or anxious); (2) neutral-tone/emotional-content; (3) emotional-tone/incongruous emotional-content; and (4) emotional-content/incongruous emotional-tone. Participants had to ignore the emotional-content in the third condition and the emotional-tone in the fourth condition. In addition, participants were assessed with a visuospatial task (in which healthy men typically excel). Correlation coefficients were computed for associations between emotional language data, visuospatial data, IQ measures and patient variables.
Overall, on the emotional language task, patients made more errors than control subjects, and women outperformed men across diagnostic groups. Controlling for IQ revealed a significant effect on task performance in all groups, especially in the incongruent tasks. On the rotation task, healthy men outperformed healthy women, but male patients, female patients and female controls obtained similar scores.
The advantage in emotional prosodic and semantic processing in healthy women is preserved in schizophrenia, whereas the male advantage in visuospatial processing is lost. These findings may explain, in part, why social functioning is less compromised in women with schizophrenia than in men.