Global brain asymmetry is increased in schizophrenia and related to avolition.

OBJECTIVE: Schizophrenia may be the result of a failure of the normal lateralization process of the brain. However, whole-brain asymmetry has not been assessed up to date. Here, we propose a novel measure of global brain asymmetry based on the Dice coefficient to quantify similarity between brain hemispheres. METHOD: Global gray and white matter asymmetry was calculated from high-resolution T1 structural images acquired from 24 patients with schizophrenia and 26 healthy controls, age- and sex-matched. Some of the analyses were replicated in a much larger sample (n = 759) obtained from open-access online databases. RESULTS: Patients with schizophrenia had more global gray matter asymmetry than controls. Additionally, increased gray matter asymmetry was associated with avolition, whereas the inverse relationship was found for anxiety at a trend level. These analyses were replicated in a larger sample and confirmed previous results. CONCLUSION: Our findings suggest that global gray matter asymmetry is related to the concept of developmental stability and is a useful indicator of perturbations during neurodevelopment.

Schizophrenia patients with high intelligence: A clinically distinct sub-type of schizophrenia?

BACKGROUND: Schizophrenia patients are typically found to have low IQ both pre- and post-onset, in comparison to the general population. However, a subgroup of patients displays above average IQ pre-onset. The nature of these patients' illness and its relationship to typical schizophrenia is not well understood. The current study sought to investigate the symptom profile of high-IQ schizophrenia patients. METHODS: We identified 29 schizophrenia patients of exceptionally high pre-morbid intelligence (mean estimated pre-morbid intelligence quotient (IQ) of 120), of whom around half also showed minimal decline (less than 10 IQ points) from their estimated pre-morbid IQ. We compared their symptom scores (SAPS, SANS, OPCRIT, MADRS, GAF, SAI-E) with a comparison group of schizophrenia patients of typical IQ using multinomial logistic regression. RESULTS: The patients with very high pre-morbid IQ had significantly lower scores on negative and disorganised symptoms than typical patients (RRR=0.019; 95% CI=0.001, 0.675, P=0.030), and showed better global functioning and insight (RRR=1.082; 95% CI=1.020, 1.148; P=0.009). Those with a minimal post-onset IQ decline also showed higher levels of manic symptoms (RRR=8.213; 95% CI=1.042, 64.750, P=0.046). CONCLUSIONS: These findings provide evidence for the existence of a high-IQ variant of schizophrenia that is associated with markedly fewer negative symptoms than typical schizophrenia, and lends support to the idea of a psychosis spectrum or continuum over boundaried diagnostic categories.

Decreased processing speed might account for working memory span deficit in schizophrenia, and might mediate the associations between working memory span and clinical symptoms.

OBJECTIVE: Verbal working memory span is decreased in patients with schizophrenia, and this might contribute to impairment in higher cognitive functions as well as to the formation of certain clinical symptoms. Processing speed has been identified as a crucial factor in cognitive efficiency in this population. We tested the hypothesis that decreased processing speed underlies the verbal working memory deficit in patients and mediates the associations between working memory span and clinical symptoms. METHOD: Forty-nine schizophrenia inpatients recruited from units for chronic and acute patients, and forty-five healthy participants, were involved in the study. Verbal working memory span was assessed by means of the letter-number span. The Digit Copy test was used to assess motor speed, and the Digit Symbol Substitution Test to assess cognitive speed. RESULTS: The working memory span was significantly impaired in patients (F(1,90)=4.6, P<0.05). However, the group difference was eliminated when either the motor or the cognitive speed measure was controlled (F(1,89)=0.03, P=0.86, and F(1,89)=0.03, P=0.88). In the patient group, working memory span was significantly correlated with negative symptoms (r=-0.52, P<0.0001) and thought disorganisation (r=-0.34, P<0.025) scores. Regression analyses showed that the association with negative symptoms was no longer significant when the motor speed measure was controlled (ß=-0.12, P=0.20), while the association with thought disorganisation was no longer significant when the cognitive speed measure was controlled (ß=-0.10, P=0.26). CONCLUSIONS: Decrement in motor and cognitive speed plays a significant role in both the verbal working memory impairment observed in patients and the associations between verbal working memory impairment and clinical symptoms.

Source memory errors in schizophrenia, hallucinations and negative symptoms: a synthesis of research findings.

BACKGROUND: Previous research has shown associations between source memory errors and hallucinations in patients with schizophrenia. We bring together here findings from a broad memory investigation to specify better the type of source memory failure that is associated with auditory and visual hallucinations. METHOD: Forty-one patients with schizophrenia and 43 healthy participants underwent a memory task involving recall and recognition of lists of words, recognition of pictures, memory for temporal and spatial context of presentation of the stimuli, and remembering whether target items were presented as words or pictures. RESULTS: False recognition of words and pictures was associated with hallucination scores. The extra-list intrusions in free recall were associated with verbal hallucinations whereas the intra-list intrusions were associated with a global hallucination score. Errors in discriminating the temporal context of word presentation and the spatial context of picture presentation were associated with auditory hallucinations. The tendency to remember verbal labels of items as pictures of these items was associated with visual hallucinations. Several memory errors were also inversely associated with affective flattening and anhedonia. CONCLUSIONS: Verbal and visual hallucinations are associated with confusion between internal verbal thoughts or internal visual images and perception. In addition, auditory hallucinations are associated with failure to process or remember the context of presentation of the events. Certain negative symptoms have an opposite effect on memory errors.

Hallucinations and two types of free-recall intrusion in schizophrenia.

BACKGROUND: Previous research has demonstrated that various types of verbal source memory error are associated with positive symptoms in patients with schizophrenia. Notably, intrusions in free recall have been associated with hallucinations and delusions. We tested the hypothesis that extra-list intrusions, assumed to arise from poor monitoring of internally generated words, are associated with verbal hallucinations and that intra-list intrusions are associated with global hallucination scores. METHOD: A sample of 41 patients with schizophrenia was administered four lists of words, followed by free recall. The number of correctly recalled words and the number of extra- and intra-list intrusions were tallied. RESULTS: The verbal hallucination score was significantly correlated with the number of extra-list intrusions, whereas it was unrelated to the number of correctly recalled words. The number of intra-list intrusions was significantly correlated with the global, but not with the verbal, hallucination score in the subsample of hallucinating patients. It was marginally significantly correlated with the delusion score in delusional patients. CONCLUSIONS: The data corroborate the view that verbal hallucinations are linked to defective monitoring of internal speech, and that errors in context processing are involved in hallucinations and delusions.

Affective modulation of external misattribution bias in source monitoring in schizophrenia.

BACKGROUND: 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. METHOD: 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. RESULTS: 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. CONCLUSIONS: Affective modulation of the externalizing cognitive bias in source monitoring is evident in patients with hallucinations and delusions.

Medications and verbal memory impairment in schizophrenia: the role of anticholinergic drugs.

BACKGROUND: We wished to assess the effect of three types of medication on verbal memory impairments in schizophrenia. METHOD: Forty-eight patients with schizophrenia and 40 healthy control subjects underwent a battery of verbal memory tasks, including free recall, recognition and short-term memory span. All the patients were on antipsychotic medication. In addition, 24 were taking anticholinergic drugs (benztropine) and 30 were taking benzodiazepines. A subsample of 39 had clinical ratings for depressive symptoms. Regression analyses were conducted on the memory measures in this subsample, with negative symptoms, depression, type of antipsychotic medication (conventional v. atypical), benzodiazepines and anticholinergic drugs as predictors. RESULTS: Type of antipsychotic medication made no significant contribution to memory deficits and benzodiazepine use made very little contribution. However, anticholinergic medication was a predictor of memory impairment, especially with regard to semantic organization. Complementary analyses revealed that patients taking any type of drug with anticholinergic activity (benztropine and/or antipsychotic agents) were significantly impaired relative to the other patients on measures reflecting free recall efficiency and semantic organization. CONCLUSIONS: Drugs with anticholinergic activity are the major pharmacological agents that contribute to the verbal memory deficit observed in patients with schizophrenia. These drugs appear to act by impeding semantic organization at encoding.

Working memory, language comprehension, and aging: four experiments to understand the deficit.

Four experiments were carried out to investigate working-memory capacity and functioning in young and older subjects, and its relation with reading comprehension. Experiment 1 showed that older subjects had to trade off processing and storage functions, due to an assumed reduced pool of resources relative to young subjects. Working-memory measures were weakly correlated with reading comprehension in each age group. Experiment 2 revealed a specific processing impairment in older subjects, and showed that older subjects tended to sacrifice the maintenance of the concurrent mnemonic load to devote more resources to ongoing processing. In Experiment 3, the age-related differences in the processing/storage trade-off were again observed. Furthermore, differences in the speed/accuracy trade-off were revealed. Experiment 4 showed that whatever the instructions regarding the speed/accuracy trade-off, the older subjects remained slower and slightly more accurate than the young subjects. In conclusion, it appears that the age-related differences in working memory are both structural and functional. Different strategies may be implemented in each age group to deal with reading comprehension.

Clinical and cognitive factors associated with verbal memory task performance in patients with schizophrenia.

OBJECTIVE: The authors have previously shown the role of depression, slowing of processing speed, and selective attention deficit in verbal memory task performance in schizophrenia. They wished to determine the specific contribution of each of these factors to various types of memory impairment. METHOD: The negative symptom score from the Positive and Negative Syndrome Scale, the Hamilton Depression Rating Scale score, a measure of processing speed, and a measure of selective attention were entered as predictors in regression analyses. Furthermore, analyses of covariance were conducted on the memory measures to test the significance of the differences between schizophrenic patients and healthy comparison subjects after control for processing speed and selective attention. RESULTS: Depression was associated only with deep encoding reflected by semantic clustering. Selective attention was associated only with superficial encoding reflected by serial recall. Slowing of processing speed was associated with both deep and superficial encoding. Negative symptoms were not associated with memory impairment except for the avolition item from the Scale for the Assessment of Negative Symptoms. Processing speed accounted for all the group differences on the memory measures that reflected superficial encoding. In addition, a subgroup of patients with no or minor depression was not significantly impaired on deep encoding relative to the healthy comparison group. CONCLUSIONS: The authors suggest that verbal memory impairment in schizophrenia is a consequence of depression and slowness, rather than a primary feature of the disease.

Language processing, slowing, and speed/accuracy trade-off in the elderly.

Previous studies have suggested that longer response times in older adults could be partly due to increased caution in responding, with a propensity to emphasize accuracy to the detriment of speed. A study was carried out in 30 young and 30 older adults in order to determine whether shifting the response criterion relative to the speed/accuracy trade-off towards a more risky strategy would significantly reduce age-related differences in response time. The experimental procedure involved the detection of incongruous sentences, either with or without a mnemonic preload. Instructions emphasized alternatively speed or accuracy. Results showed that whatever the instructions, older adults remained consistently much slower than young adults, and a little more accurate. When instructed to emphasize speed, they never managed to reduce the response time difference relative to young adults. It is concluded that the more cautious approach in older adults is required to attenuate the adverse effects of a slower processing system.

Positive symptomatology and source-monitoring failure in schizophrenia--an analysis of symptom-specific effects.

Recent research has suggested that certain positive symptoms in patients with schizophrenia are linked to self monitoring/reality-monitoring deficits. We wished to investigate the association between such deficits and three specific symptoms: hallucinations, delusions and thought disorganisation. Forty patients with schizophrenia and 40 normal controls were administered a source-monitoring task. Twenty-four items were produced, either verbally by the experimenter, or verbally by the subject, or presented as pictures. Then, subjects were read a recognition list including the produced target items mixed with distractors. They were required to recognise the target items and to remember their source of production. The pattern of memory deficits has previously been reported (Brébion, G., Smith, M., Gorman, J., Amador, X., 1997. Discrimination accuracy and decision biases in different types of reality monitoring in schizophrenia. Journal of Nervous and Mental Disease 185, 247-253). The current analyses focussed on the false recognition of distractors, and on the errors in the source attribution of the recognised target items. Results showed that higher hallucination scores were associated with an increased tendency towards false recognition of non-produced items. In addition, hallucinators were more prone than control subjects to misattribute to another source the items they had produced themselves. Furthermore, hallucinators and delusional patients were more prone than the other patients to report that spoken items had been presented as pictures. This latter finding suggests that both hallucinations and delusions are associated with confusion between imagined and perceived pictures. Our previous report stated that only one of the three investigated types of response bias was associated with global positive symptomatology. However, this finer-grained analysis revealed that the three of them were in fact associated with hallucinations and/or delusions. On the other hand, thought disorganisation appeared to be independent from these mechanisms.

Depression, psychomotor retardation, negative symptoms, and memory in schizophrenia.

OBJECTIVE: The purpose of this study was to examine the relations between depression, psychomotor retardation, and negative symptoms in schizophrenia as well as the specific contribution of each of these factors to memory impairment. BACKGROUND: It has been suggested that depression overlaps with negative symptomatology in schizophrenia. The relation between psychomotor retardation and negative symptomatology has been unclear. METHOD: The Hamilton Depression Rating Scale, The Positive and Negative Symptom Scale for Schizophrenia, and Scale for the Assessment of Negative Symptoms were used to assess depressive and negative symptomatology in a sample of patients with schizophrenia. Verbal memory performance was assessed by a free recall test. Two indices of processing speed were measured. Correlations among variables were computed. RESULTS: Depression score was correlated with the avolition item from the Scale for the Assessment of Negative Symptoms and with both measures of processing speed. Negative symptomatology was unrelated to processing speed. Memory performance was correlated with depression score, slowing of processing speed, and avolition. Its correlation with depression score and processing speed remained significant when the other factors were partialled out. CONCLUSIONS: Memory performance in schizophrenia may be affected by lack of motivation, psychomotor retardation, and depression. It is suggested that negative symptoms could be split between a volitional component linked to depression and cognitive efficiency and an emotional component unrelated to them.

Memory and schizophrenia: differential link of processing speed and selective attention with two levels of encoding.

The purpose of this study was to investigate how underlying cognitive deficits such as a defect in processing speed or in selective attention contributed to different types of memory impairment observed in schizophrenia (superficial vs deep encoding). 49 schizophrenic patients and 40 normal controls were administered a verbal memory task. Superficial encoding was assessed by the ability to recall items in their serial order. Deep encoding was assessed by the ability to organise words into semantic categories. Two measures of processing speed (Digit Symbol Substitution Test and Stroop colour time) and one measure of selective attention (Stroop test) were used. Regression analyses were carried out. In the patient group, processing speed contributed to both superficial and deep encoding, and to a global verbal memory score. Selective attention only contributed to the superficial encoding processes. Thus, slowing of processing speed in schizophrenia seems to be more crucial for memory performance, since it affects memory in a pervasive way.

Opposite links of positive and negative symptomatology with memory errors in schizophrenia.

We wished to confirm and extend a previous correlational study of our group, suggesting that positive symptoms in schizophrenia were linked to an increase in certain types of memory errors, and negative symptoms to a decrease in other types of errors. A post-hoc analysis was conducted in 33 schizophrenic patients and 40 normal control subjects on memory errors collected in a free recall task and two types of recognition tasks. The memory errors were intrusions and list errors in free recall, and decision bias towards false alarms in recognition, all assumed to reflect a source-monitoring failure. In a first analysis, the patient sample was split along the median for positive symptoms as rated by the Scale for the Assessment of Positive Symptoms (SAPS). In a second analysis, it was split along the median for negative symptoms as rated by the Scale for the Assessment of Negative Symptoms (SANS). Patients with high ratings of positive symptoms made more memory errors (intrusions, list errors, false alarms) than those with low ratings, supporting the hypothesis of a link between positive symptomatology and source-monitoring failure. On the other hand, patients with high ratings of negative symptoms made fewer of these errors than the other patients. Fewer errors were specifically associated with more affective flattening, alogia and anhedonia, whereas avolition was entirely unrelated to them.

Word recognition, discrimination accuracy, and decision bias in schizophrenia: association with positive symptomatology and depressive symptomatology.

The purpose of this experiment was to replicate and extend to a memory task Bentall and Slade's (1985) finding that hallucinations in schizophrenic patients were linked to a liberal decision bias. A word recognition task was administered to 40 schizophrenic patients and 40 normal controls that yielded two indices of performance: an index of discrimination accuracy (Pr) and one of decision bias (Br). Patients obtained a lower Pr than controls, whereas Br was similar in both groups. In patients, Br was selectively correlated with positive symptomatology: the more the positive symptoms, the more liberal the bias. In particular, there was a specific correlation between decision bias and hallucinations. Conversely, Pr was inversely correlated with severity of depression, but not with either positive or negative symptoms. Thus, positive symptomatology may be linked more to difficulties in distinguishing between representations of internal versus external events than to deficits in encoding external events.

Memory impairment and schizophrenia: the role of processing speed.

A link between slowing of processing speed and cognitive disorders, including memory, has repeatedly been found in research on aging, and suggested in other cognitively impaired populations. We tested the hypothesis that a link between memory impairment and slowing of processing speed would also be observed in schizophrenia. Forty-four schizophrenic patients and 40 normal controls were administered a memory task involving free recall and recognition. Processing speed was assessed by the Digit Symbol Substitution Test. Working memory span was assessed as well. The measure of processing speed was consistently correlated with the various memory measures in patients, including efficiency of encoding. These correlations remained significant, or tended to be significant, when working memory span was partialled out. Memory deficits observed in schizophrenia may thus be partly accounted for by a slowing of processing speed. It is suggested that research on cognitive deficits in this and other mental diseases focus more on processing speed.

Effects of clozapine on plasma catecholamines and relation to treatment response in schizophrenia: a within-subject comparison with haloperidol.

We conducted a within-subject comparison of the effects of clozapine and haloperidol on plasma levels of neurotransmitters and metabolites, and related changes in specific plasma neurochemicals with clozapine response. The subjects were 14 inpatients with schizophrenia or schzoaffective disorder, who were refractory to haloperidol and at least one other typical antipsychotic medication. Subjects underwent, in the following order: a 6-week "fixed, flexible dose" haloperidol trial, followed by a 2-4 week medication-free phase, and a 6-week clozapine trial. Plasma levels of norepinephrine (NE), homovanillic acid (HVA), and 3-methoxy-4-hydroxyphenylglycol (MHPG), and objective clinical ratings of total, positive, negative, and depressive symptoms were obtained at the end of each phase. As expected, we found a substantial increase of plasma NE with clozapine but not with haloperidol. However, the increase in NE was not associated with improvement in total or positive symptomatology. There was some evidence for an association between improvement in negative symptoms and increased HVA on clozapine, as well as diminished HVA during the medication-free phase. The implications of these data for understanding the mechanisms of action of clozapine are discussed.

Clinical correlates of memory in schizophrenia: differential links between depression, positive and negative symptoms, and two types of memory impairment.

OBJECTIVE: This study investigated clinical correlates of memory impairment in schizophrenic patients. In particular, the authors hypothesized that depressive symptoms would be linked to memory efficiency, as found in other clinical populations. In addition, they tested Frith's pathophysiological model predicting links between negative symptoms and failure to respond, as well as between positive symptoms and production of erroneous responses. METHOD: Thirty-one patients were given several memory tasks: long-term free recall of nonorganizable and organizable lists in immediate and delayed conditions, recognition in immediate and delayed conditions, implicit memory (stem completion task), and short-term memory (digit span). Superficial encoding of information was also assessed by the ability to recall the items sequentially; deep encoding was assessed by the ability to organize the items according to their semantic properties. Two types of memory measures were individualized: measures reflecting memory efficiency and measures reflecting production of erroneous memory responses (intrusions, perseverations, false alarms). RESULTS: Consistent correlations appeared between severity of depressive symptoms and measures reflecting deep but not superficial encoding; none, however, was correlated with negative symptoms. Two of the three types of erroneous memory responses were positively linked to positive symptoms. CONCLUSIONS: Efficiency of memory processes relying on deep encoding seemed linked to depressive symptoms. In addition, the two distinct types of impairment predicted by Frith's model were found. The expected link of one with positive symptoms was verified, but the link of the other with negative symptoms was not.

Discrimination and response bias in memory: effects of depression severity and psychomotor retardation.

Although memory disorders have been well documented in depression, there is controversy concerning depressives' performance on recognition memory tasks; e.g. whether they have impaired discrimination and conservative or liberal response bias according to signal detection theory. In addition, symptomatic correlates of discrimination and response bias indices have been lacking. A word recognition memory task analyzed according to the two high threshold theory was administered to 26 depressives and 26 controls. Depressives obtained a lower index of discrimination (Pr) than controls. The index of response bias (Br) was not different between groups. In the depressed group, overall severity of depression was related to discrimination, whereas psychomotor retardation level was related to response bias. Cognitive performance of depressives could be advantageously analyzed in terms of these two dimensions of symptomatology.

Discrimination accuracy and decision biases in different types of reality monitoring in schizophrenia.

A reality monitoring task was administered to 31 schizophrenic patients and 31 normal controls. Twenty-four items were produced, either orally by the experimenter, orally by the subjects, or seen as pictures. Subjects were later read a list of 48 items and were asked to indicate if each item was new, self-generated, experimenter-generated, or presented as a picture. Results showed that schizophrenic patients were impaired in discriminating old items from new, with a higher bias than controls toward reporting new items as if they were old (false alarms). In addition, patients were impaired in discriminating self-generated items from externally generated items, with a higher bias than controls toward attributing self-generated items to an external source. Lastly, they were significantly impaired in discriminating the modality (auditory versus visual) in which the event was presented. The bias toward remembering orally produced items as pictures was correlated with positive symptomatology and was significantly higher than controls in patients with high levels of positive symptoms. This suggests that mental imagery may play a role in positive symptomatology. These results demonstrate the relevance of studying decision biases along with discrimination performance for the understanding of the mechanisms of reality monitoring impairment in schizophrenia.