P.D. Harvey

Correlates of insight in first episode psychosis

Impaired insight is common in schizophrenia and may be related to poor treatment adherence. Few studies have examined the clinical and neurocognitive correlates of insight in early schizophrenia. Early course schizophrenia, schizoaffective, and schizophreniform disorder patients (n=535) were studied. The Positive and Negative Symptom Scale (PANSS) was used to assess psychopathology, and a broad range of neuropsychological functions was assessed. Using hierarchical stepwise multiple regression analyses, we examined the association of clinical, neurocognitive, and premorbid measures with the level of insight. Impaired insight was associated with overall symptomatology, including positive, negative, and general psychopathology and with deficits in cognitive functioning. In descending order of robustness, the significant variables were PANSS general psychopathology (p<0.0001), Rey Auditory Verbal Learning Test (p<0.0004), Clinical Global Impression (p<0.005), PANSS positive (p<0.007), and premorbid adjustment-general subscale (p=0.02). Among the PANSS general psychopathology items, unusual thought content was most robustly associated with impaired insight (p<0.00000). Insight impairment is very common in early schizophrenia, and appears to be associated with a broad range of psychopathology and deficits in multiple cognitive domains. These observations suggest that deficits in insight may be related to a generalized dysfunction of neural networks involved in memory, learning, and executive functions.

Klinefelter's Syndrome (XXY) as a Genetic Model for Psychotic Disorders

Males with an extra‐X chromosome (Klinefelters syndrome) frequently, although not always, have an increased prevalence of psychiatric disturbances that range from attention deficit disorder in childhood to schizophrenia or severe affective disorders during adulthood. In addition, they frequently have characteristic verbal deficits. Thus, examining brain magnetic resonance imaging (MRI) scans of these individuals may yield clues to the influence of X chromosome genes on brain structural variation corresponding to psychiatric and cognitive disorders. Eleven adult XXY and 11 age matched XY male controls were examined with a structured psychiatric interview, battery of cognitive tests, and an MRI scan. Ten of eleven of the XXY men had some form of psychiatric disturbance, four of whom had auditory hallucinations compared with none of the XY controls. Significantly smaller frontal lobe, temporal lobe, and superior temporal gyrus (STG) cortical volumes were observed bilaterally in the XXY men. In addition, diffusion tensor imaging (DTI) of white matter integrity resulted in four regions of reduced fractional anisotropy (FA) in XXY men compared with controls, three in the left hemisphere, and one on the right. These correspond to the left posterior limb of the internal capsule, bilateral anterior cingulate, and left arcuate bundle. Specific cognitive deficits in executive functioning attributable to frontal lobe integrity and verbal comprehension were noted. Thus, excess expression of one or more X chromosome genes influences both gray and white matter development in frontal and temporal lobes, as well as white matter tracts leading to them, and may in this way contribute to the executive and language deficits observed in these adults. Future prospective studies are needed to determine which gene or genes are involved and whether their expression could be modified with appropriate treatments early in life. Brain expressed genes that are known to escape inactivation on extra‐X chromosomes would be prime candidates.

A long-term, multicenter, open-label study of risperidone in elderly patients with psychosis

Studies have shown that risperidone is safe and efficacious in young and middle‐aged adults with chronic schizophrenia, but considerably fewer data are availabale on the treatment of elderly patients with schizophrenia or other psychotic disorders, particularly long‐term outcomes.

Neuropsychological performance in schizotypal personality disorder: evidence regarding diagnostic specificity

BACKGROUND Individuals with schizotypal personality disorder (SPD) share cognitive deficits with schizophrenic patients, suggesting that these deficits represent a core feature of the schizophrenia spectrum. We investigated the neuropsychological profile in SPD patients compared with two comparison groups: healthy volunteers (HV) and patients who met criteria for another non-schizophrenia spectrum personality disorder (NSS). METHODS We tested 48 DSM-III-R SPD patients, 22 NSS and 32 HV on a neuropsychologic battery that included the California Verbal Learning Test (CVLT), Trail Making A and B, the DOT test of working memory, the Stroop Color-Word Interference, the Paced Auditory Serial Addition Test (PASAT), the Wechsler Memory Scale Visual Reproduction Test (WMSV-R), and the Wechsler Adult Intelligence Scale vocabulary and block design. RESULTS Normative standards for performance were created using the HV group. SPD patients performed significantly worse compared with HVs; specifically, SPD patients demonstrated impaired performance on the PASAT and the WMSV-R immediate and delayed recall compared to HV. Moreover, SPD patients were impaired in the PASAT and the WMSV-R immediate condition compared with the NSS group. The NSS patients did not differ from HV on any of the cognitive tasks. The interpersonal factor of the schizotypal symptoms inversely correlated with the PASAT score (r = -.32, p <.006). CONCLUSIONS Compared with HVs, SPD patients demonstrate modest cognitive impairment. These differences reached statistical significance for the PASAT (an auditory working memory task), and the WMSV-R immediate and delayed recall (a learning-recall test). In contrast, performance of NSS patients did not differ from that of HVs. The types of deficits observed in SPD patients are qualitatively similar to but milder than those seen in patients with schizophrenia.

Cognitive assessment of geriatric schizophrenic patients with severe impairment.

There is evidence that some elderly patients with chronic schizophrenia experience marked impairments in cognitive functioning. Assessment of these patients may be difficult with traditional neuropsychological measures. The purpose of the present study was to determine if cognitive functioning could be validly assessed with the Alzheimers Disease Assessment Scale-Late Version Cognitive factor score (ADAS-L Cog) in patients whose scores on the Mini-Mental State Examination (MMSE) reflect profound cognitive impairment. Patients with MMSE scores from 0 to 10 were selected from a larger database. Neuropsychological instruments designed for the assessment of mild to moderate dementia were found to be inadequate in this profoundly impaired population, due to floor effects. In contrast, there was a significant relationship between ADAS-L scores and several criterion measures, including the MMSE (R=-.71, P<.001), the Social Adaptive Functions Evaluation (SAFE) social functions scale (R=.47, P<.001), and the negative symptom total score of the Positive and Negative Syndrome Scale (PANSS) (R=.412, P<.001). The MMSE was somewhat less strongly correlated with both social functions (R=-.401, P<.001) and the negative symptom total score of the PANSS (R=-.366, P<.001). These results suggest that cognition can be reliably and validly assessed with instruments such as the ADAS-L that are designed for the assessment of severely impaired patients.

A comprehensive analysis of verbal fluency deficit in geriatric schizophrenia.

Deficits in verbal fluency are common in schizophrenia and may provide keys to some of the abnormalities in the semantic system in schizophrenia. While a number of studies have outlined the severity and implications of verbal fluency deficits in younger schizophrenia patients, these findings have not yet been extended to older patients with schizophrenia. In this study, 392 older (age >/= 50) patients with schizophrenia were administered phonological and semantic (i.e., category) fluency examinations, as well as tests of learning, memory, language, and praxic skills, and rated for clinical symptoms and functional status. When compared to normative standards, 82% of the patients were impaired in semantic fluency and 83% were impaired in phonological fluency. Both semantic and phonological fluency impairment were significantly correlated with other cognitive variables, total scores on the functional status measure, and with the social and self-care subscales. Scores were uncorrelated with the severity of psychosis, but were correlated with the severity of negative symptoms. Furthermore, the severity of poverty of speech (a clinical measure of verbal underproductivity) was moderate in magnitude and failed to enter as a predictor of verbal fluency, indicating that impaired fluency scores are not simply an artifact of general underproductivity or mutism. The findings support conclusions from studies with younger schizophrenia patients that suggest that verbal fluency impairment is a consequence of a disorganized semantic system. Verbal fluency impairment remains common and functionally relevant in schizophrenia patients in late life.

The Use of Antihistamines in Safety-critical Jobs: A Meeting Report *

Summary The use of sedating agents by aircrew and those with safety-critical occupations has raised serious concern and has been extensively debated for several years. This meeting report summarizes the findings of an international panel of experts in aerospace medicine and L allergic rhinitis who were brought together to discuss issues related to the use of antihistamines, in particular the selective, H1-receptor antagonist fexofenadine, in pilots. The presentations covered a wide range of topics including methods for accurately assessing sedation and impairment, and the validity of laboratory testing versus simulator assessments. The panel also examined data on sedation and impairment levels with currently available antihistamines and assessed the impact of these data on their use by pilots and aircrew. It was the consensus of the meeting that fexofenadine can be safely recommended for use in individuals involved in skilled activities, such as pilots, without the concern of sedation above recommended therapeutic doses.

Prevalence and correlates of parkinsonism in an institutionalized population of geriatric patients with chronic schizophrenia

Geriatric patients with chronic schizophrenia are at increased risk for parkinsonism and cognitive impairment, but the relationship between the two has been insufficiently studied.

Kraepelinian schizophrenia: A replication in an independent sample

Chronic, unremitting schizophrenic patients, who for the past 5 years had been either continuously hospitalized or completely dependent on others for their survival are designated Kraepelinians according to Emil Kraepelin’s description of dementia praecox. Previous studies from our center have demonstrated that Kraepelinian patients more consistently received a diagnosis of schizophrenia across a variety of cross-sectional and longitudinal diagnostic criteria and had more severe negative symptoms and formal thought disorder compared to a group of age-matched non-Kraepelinian chronic schizophrenic patients. In addition, Kraepelinian schizophrenics had a greater morbid risk for schizophrenia spectrum disorders in their first-degree relatives, had a greater left-to-right asymmetry of their lateral cerebral ventricles, and had less of a prospective response to a standard dose of haloperidol. On the other hand, the severity of positive symptoms did not distinguish Kraepelinian schizophrenics from other chronic schizophrenic patients. This study presents data on a completely independent sample of 22 Kraepelinian and 86 non-Kraepelinian schizophrenic patients. Initial data analyses suggest a replication of the findings reported on the original cohort. Kraepelinian patients had more severe negative symptoms (p < 0.002) and formal thought disorder (p c 0.001) than non-Kraepelinian chronic schizophrenic patients. The first degree relatives of Kraepelinian patients had a greater morbid risk for schizophrenia spectrum disorders than the relatives of other chronic schizophrenic patients (z = 3.3 1, p < 0.001). CT ventricular measures indicated a left frontal horn enlargement in Kraepelinian patients relative to nonKraepelinians (p < 0.05). These analyses provide independent confirmation that Kraepelinian schizophrenic patients, who require institutionalization or institution-like care, differ from other schizophrenic patients on measures of clinical presentation and family history, suggesting that these patients are a relatively homogenous subgroup of schizophrenics with very severe symptoms and uniformly poor outcomes.

108. Neurocognitive predictors of functional decline in poor-outcome schizophrenia

Although cognitive abilities have been shown to be directly related to social, occupational, and adaptive functioning in patients with schizophrenia, there is no evidence indicating that a specific neuropsychological index can predict decline in functional status. Impairments in verbal learning and memory, verbal skills, and executive functions correlate with functional impairments, and are predictive of functional ability over time. Yet, there is no evidence that impairment on a specific neurocognitive index is associated with functional decline, or whether these measures are all associated with functional impairments due to a global or specific cognitive deficit. In order to test whether any of these neuropsychological measures (Verbal Learning and Memory, Praxis, and Confrontational Naming) is most associated with functional decline, 68 subjects were chosen from a long-term study of the effects of aging in schizophrenia. Subjects were chosen specifically because they declined functionally from a mildly impaired level of functioning to a moderate or severely impaired level of functioning across two assessments (mean interval 5 1.89 years, sd 5 1.42 years), based on a global rating of functioning on the Clinical Dementia Rating Scale (CDR). Age and education corrected z-scores were derived for measures of verbal learning, delayed memory, praxic ability, and confrontational naming, based on performance of healthy controls on these measures as part of the Consortium to Establish a Registry of Alzheimer’s Disease (CERAD). Change in performance on these neuropsychological measures was calculated by subtracting the standardized z-score of each measure at the follow-up assessment from the standardized score obtained on each measure at the initial assessment. A repeated measures ANOVA was used to determine if any of these measures were specifically associated with functional decline. Whereas the overall ANOVA was significant (F(1, 67) 5 14.49, p , .001), no specific measure of neurocognitive functioning was able to account for the decline in functional ability (Rao’s R (3, 65) 5 1.19, p , .321). These data suggest that the cognitive decline seen in these patients is generalized, rather than selective. It may be that this functional decline is related to low levels of cortical decline in patients with poor premorbid functioning and a chronic clinical course of illness.