Ann Mortimer

Memory in schizophrenia: What is impaired and what is preserved?

This study assesses the pattern of long-term memory performance in a sample of 12 schizophrenic patients who were selected on the basis of showing a memory deficit in the absence of gross overall intellectual impairment. When compared with 12 control subjects matched for age, sex and estimated premorbid IQ, presence of an episodic memory deficit was confirmed for both prose recall and forced-choice word and face recognition. Semantic memory was assessed using the sentence verification task developed by Collins and Quillian, an unpaced category judgement task, and the Mill Hill Vocabulary Scale. The schizophrenic patients were slower on sentence verification and they made significantly more errors in all three tasks. Procedural tasks included pursuit rotor performance, speed of repeatedly assembling a jigsaw puzzle and rate of improvement in reading transformed script. Here, while the schizophrenic patients showed poor overall performance on the pursuit rotor and jigsaw learning, their rate of learning on all three procedural tasks was comparable with that of the controls. When examined on two implicit memory tasks involving biasing of spelling of homophones and word stem completion, the patients showed a normal degree of priming in both. Implications for the nature of the memory deficit in schizophrenia are discussed.

Semantic memory is impaired in schizophrenia

Memory is emerging as a key area of neuropsychological deficit in schizophrenia, with evidence suggesting that the impairment is restricted to long-term memory. Semantic memory, the component of long-term memory containing stored representations of the meanings of words and knowledge about the world, was examined in 46 schizophrenic patients and 40 normal controls using a recently devised battery of tests. Evidence of semantic memory impairment was found which was wide ranging and substantial; in some cases it approached the levels seen in a group of 22 patients with mild-to-moderate Alzheimers disease. Both group analysis and a more detailed examination of two single cases suggested that semantic memory impairment represents a disproportionate and possibly specific neuropsychological deficit in schizophrenia.

Predicting suicidal risk in schizophrenic and schizoaffective patients in a prospective two-year trial

BACKGROUND Enhanced ability to reliably identify risk factors for suicidal behavior permits more focused decisions concerning treatment interventions and support services, with potential reduction in lives lost to suicide. METHODS This study followed 980 patients at high risk for suicide in a multicenter prospective study for 2 years after randomization to clozapine or olanzapine. A priori predictors related to diagnosis, treatment resistance, and clinical constructs of disease symptoms were evaluated as possible predictors of subsequent suicide-related events. RESULTS Ten baseline univariate predictors were identified. Historical predictors were diagnosis of schizoaffective disorder, history or current use at baseline of alcohol or substance abuse, cigarette smoking, number of lifetime suicide attempts, and the number of hospitalizations in the previous 36 months to prevent suicide. Predictive clinical features included greater baseline scores on the InterSePT scale for suicidal thinking, the Covi Anxiety Scale, the Calgary Depression Scale (CDS), and severity of Parkinsonism. Subsequent multivariate analysis revealed the number of hospitalizations in the previous 36 months, baseline CDS, severity of Parkinsons, history of substance abuse, and lifetime suicide attempts. Clozapine, in general, was more effective than olanzapine in decreasing the risk of suicidality, regardless of risk factors present. CONCLUSIONS This is the first prospective analysis of predictors of suicide risk in a large schizophrenic and schizoaffective population judged to be at high risk for suicide. Assessment of these risk factors may aid clinicians in evaluating risk for suicidal behaviors so that appropriate interventions can be made.

The InterSePT scale for suicidal thinking reliability and validity

BACKGROUND The InterSePT Scale for Suicidal Thinking (ISST) is a 12-item instrument for the assessment of current suicidal ideation in patients with schizophrenia and schizoaffective disorders. We report the psychometric characteristics of this new scale based on two studies. METHOD In Study 1, 22 inpatients with schizophrenia and schizoaffective disorders, who had recently attempted suicide or engaged in suicidal ideation, were rated by three trained independent raters to examine interrater reliability. In Study 2, a total of 980 patients with schizophrenia or schizoaffective disorder with a history of suicidal ideation in the past 36 months were enrolled in a 2-year industry-sponsored suicide prevention study. At baseline, these patients were administered the ISST and the Clinical Global Impression Scale for Severity of Suicidality (CGI-SS) by the Principal Investigator (PI) and by a blinded rater (BR), who also administered the Positive and Negative Symptom Scale (PANSS), the Calgary Depression Scale (CDS), and the Scale of Functioning (SOF). Indices of internal reliability, construct and discriminant validity were examined. RESULTS The intraclass correlation coefficient (ICC) for the total ISST score for the 22 subjects in Study 1 was 0.90 and mean weighted item kappa coefficients ranged from 0.66 to 0.92. In Study 2, internal reliability (Cronbach alpha) was high, ranging from 0.86 to 0.89 for the individual items, and the overall Cronbach alpha coefficient for all items was 0.88. The ISST (PI) total score was highly correlated with the CGI-SS by the blind rater (r = 0.61, p < 0.0001). ISST total scores significantly differentiated the different levels of CGI-SS (F = 519.2; p < 0.0001). Results of construct and discriminant validity analyses are also presented. CONCLUSION The ISST is a reliable and valid instrument for the assessment of current suicidal thinking in patients with schizophrenia and schizoaffective disorder by both clinicians and researchers.

Cholecystokinin messenger RNA deficit in frontal and temporal cerebral cortex in schizophrenia

No consistent markers of pathology have been established yet in schizophrenia, although abnormalities in frontal and temporal structures are indicated from positron emission tomography (PET) studies. We have used in situ hybridization to investigate functional changes focusing on the quantitation of cholecystokinin (CCK) mRNA, whose product has been shown to be depleted in schizophrenia. CCK mRNA and G(o) alpha-subunit mRNA were measured in eight schizophrenic and eight control subjects matched for age and postmortem delay. The study revealed a marked decrease in CCK mRNA of 83% in frontal cortex (BA10) and 63% in superior temporal cortex (BA22) in schizophrenia with no change in G(o) alpha-subunit mRNA in either region. This study was extended to a further series of eight patients to determine the reproducibility of this effect and to quantitate laminar changes in CCK mRNA. Quantitation of CCK mRNA in inner cortical layers (layer V/VI) was carried out in frontal and temporal cortex in comparison with G(o) alpha-subunit mRNA, which is also concentrated in this region; this study showed a similar selective decrease in CCK mRNA in frontal and temporal cortex of 47% and 51%, respectively. A confirmatory decrease in CCK mRNA was also obtained by slot blot analysis of CCK mRNA in tissue extracts of frontal cortex by reference to levels of beta-tubulin mRNA, CCK mRNA:beta-tubulin mRNA was significantly decreased (67%) in schizophrenic tissue compared to control tissue. There was no significant correlation of CCK mRNA loss with neuroleptic treatment or duration of illness.

Dimensionen der Schizophrenie im Alter Korrelationen mit kognitiven und motorischen Auffälligkeiten

In most factor analytical studies of schizophrenic symptomatology a three-factor solution was found. The aim of this study was to investigate symptomatological dimensions in old age and to clarify whether the dimensions correlate differently with neuropsychological and motor parameters. A total of 131 DSM-III-R schizophrenics (mean age 68 years) were assessed using SANS, SAPS, a neuropsychological test battery and motor scales. A factor analysis yielded three dimensions (negative, disorganized, paranoid), two of which (negative, disorganized) showed different correlations with neuropsychological and motor phenomena. Thus, three symptomatological dimensions could also be demonstrated in a chronic, old-age schizophrenic sample. The pathophysiological significance of the different correlations with neuropsychological and motor parameters should be clarified in neuroimaging and neuropathological studies.ZusammenfassungIn den meisten faktorenanalytischen Studien der schizophrenen Symptomatik wurde eine 3-Faktoren-Lösung gefunden. Ziel dieser Studie war es, die symptomatologischen Dimensionen der Schizophrenie im Alter zu untersuchen und zu prüfen, ob die verschiedenen Dimensionen unterschiedlich mit kognitiven und motorischen Parametern korrelieren. 131 gemäß DSM-III-R chronisch schizophrene Patienten (Alter x–=68 Jahre) wurden mittels SANS, SAPS, einer neuropsychologischen Testbatterie und motorischen Skalen untersucht. Die Faktorenanalyse der Symptomatik ergab 3 Dimensionen (negativ, desorganisiert, paranoid-halluzinatorisch). Der negative und desorganisierte Faktor korrelierten signifikant unterschiedlich mit neuropsychologischen und motorischen Auffälligkeiten. Auch bei chronischen, altgewordenen Schizophrenen lassen sich somit 3 symptomatologische Dimensionen nachweisen. Die pathophysiologische Bedeutung der unterschiedlichen Korrelationen mit den neuropsychologischen und motorischen Parametern sollte in bildgebenden und neuropathologischen Studien abgeklärt werden.SummaryIn most factor analytical studies of schizophrenic symptomatology a three-factor solution was found. The aim of this study was to investigate symptomatological dimensions in old age and to clarify whether the dimensions correlate differently with neuropsychological and motor parameters. A total of 131 DSM-III-R schizophrenics (mean age 68 years) were assessed using SANS, SAPS, a neuropsychological test battery and motor scales. A factor analysis yielded three dimensions (negative, desorganized, paranoid), two of which (negative, disorganized) showed different correlations with neuropsychological and motor phenomena. Thus, three symptomatological dimensions could also be demonstrated in a chronic, old-age schizophrenic sample. The pathophysiological significance of the different correlations with neuropsychological and motor parameters should be clarified in neuroimaging and neuropathological studies.

Current and future treatment modalities in schizophrenia: novel antipsychotic drugs and cognitive therapy

In 60 years of use of antipsychotic drugs in schizophrenia, the only definite advance has been the introduction of clozapine. Some but not all other atypical or second-generation drugs may have small therapeutic advantages over conventional antipsychotics, but this remains controversial. New entrant atypicals seem unlikely to be therapeutically superior to conventional drugs, and glutamatergic drugs have yet to fulfill their theoretical promise. There is considerable current interest in novel mechanisms of antipsychotic action, but no such drugs have yet reached market authorization. A psychotherapeutic intervention, cognitive behavioral therapy has also found a place in the treatment of schizophrenia. However, the size of its effect against psychotic symptoms is small, and current evidence suggests no effect against negative symptoms or in reducing relapse.

Cognition in Schizophrenia: Impairments, Importance and Treatment Strategies

This multi-author volume suffers from both the fragmentation and the duplication to which such works are prone. It begins with accounts of several cognitive domains thought to be relevant to schizophrenia but there is no section that places these separate domains within an overall context. A