Electroretinogram and cue-elicited craving in withdrawn cocaine-dependent patients: a replication.

BACKGROUND: We previously reported that cocaine-dependent patients with a reduced blue cone b wave electroretinogram (ERG) responses had significantly more cue-elicited craving. METHODS: A new series of 21 recently withdrawn cocaine-dependent patients completed a craving questionnaire at baseline and following cue exposure; an ERG was also performed. RESULTS: Cocaine-dependent patients with a blunted ERG blue cone response (<0.5 microV) showed greater increases in craving following cue exposure. When subjects were included from our preliminary study (N = 14), these differences became highly significant. CONCLUSIONS: Patients with a reduced ERG response may represent a subgroup more vulnerable to cocaine craving and future relapse.

The efficacy and safety of clozapine versus chlorpromazine in geriatric schizophrenia.

BACKGROUND: There has been an absence of controlled studies focusing specifically on neuroleptic treatment in the elderly schizophrenic population. Therefore, we conducted a 12-week double-blind comparison study to assess the efficacy and tolerability of clozapine and chlorpromazine in a group of elderly inpatients with chronic schizophrenia. METHOD: Forty-two elderly DSM-IV schizophrenic veterans were randomly assigned to clozapine or chlorpromazine and assessed for efficacy at baseline and at termination with the Positive and Negative Syndrome Scale (PANSS) and the Clinical Global Impressions scale (CGI). Side effects were also monitored. Medications were titrated, on the basis of clinical response and side effects, to a maximum dose of 300 mg/day of clozapine or 600 mg/day of chlorpromazine. RESULTS: The results suggest that both the chlorpromazine and clozapine groups improved their PANSS scores at termination compared with baseline, but the difference between the 2 groups was not statistically significant. The mean CGI scores reflecting severity of illness also demonstrated improvement in both groups over time. Both groups had similar incidences of side effects. One patient in each group had a life-threatening side effect. More patients taking clozapine had tachycardia and weight gain, while more chlorpromazine patients noted sedation. CONCLUSION: We concluded that both clozapine and chlorpromazine are effective treatments for psychosis and behavioral disturbances in geriatric schizophrenia. Both agents had similar incidences of side effects. With careful monitoring and titration of dosage, both clozapine and chlorpromazine were fairly well tolerated in this population.

Comparison of linear equating and prorated short forms for estimating WAIS-R FSIQ in a neuropsychological population.

Comparisons were made of estimates of the Wechsler Adult Intelligence Scale - Revised Full Scale IQ using the two-,three- and four-subtest linear equating procedures of Kaufman (1990) and Booker and Cyr (1986) with FSIQ estimates using prorating to obtain FSIQ scores. The advantage of prorating is that it affords greater clinical flexibility in selection of subtests. The participants were 64 neuropsychiatric patients who completed the full WAIS-R from which short form and FSIQ were calculated. Prorating yielded estimates of mean IQ and categorization of IQ comparable to IQs obtained by linear equating, though there was an increased likelihood of disparate results with extreme IQ scores. Prudent clinical judgment is recommended for situations involving unusual or extreme scaled score patterns, particularly when the number of subtests is small.

Factor structure of the Neurobehavioral Cognitive Status Exam (COGNISTAT) in healthy, and psychiatrically and neurologically impaired, elderly adults.

This study reports the results of factor analyses of COGNISTAT (NCSE) in a sample of elderly persons comprised of "healthy" participants with no psychiatric or neurological impairments (n = 153), individuals with psychiatric impairments (n = 70), and those with neurological impairments (n = 80). Our findings support a unitary factor structure for COGNISTAT, though a separate factor of unclear clinical or theoretical significance was suggested.

Computerized self-assessment of psychosis severity questionnaire [COSAPSQ] in schizophrenia: preliminary results.

We attempted to develop and validate a computer-driven patient self-rated questionnaire [COSAPSQ] which should provide a reliable, rapid, and inexpensive method to assess symptom severity in patients with psychosis in general and with schizophrenia in particular. After giving informed consent patients with DSM-IV schizophrenia or schizoaffective disorder were interviewed and rated on PANSS and CGI. Subsequently patients completed the COSAPSQ questionnaire (61 multiple choice questions) in the presence of an observer. The analysis of the first 29 rating sets showed that patients with CGI scores of 3-6 completed the questionnaire in a mean time of 21.6 minutes. One-way analysis of variance of COSAPSQ total scores by CGI ratings was highly significant (p < .001). COSAPSQ total scores correlated well with PANSS total, general and positive scores and with CGI (all r = 6-.7; p < .005). The next versions of the questionnaire will require some adjustments: overall fewer questions, improved assessment of negative symptoms, and improved graphic presentation.

Obsessions and compulsions as a distinct cluster of symptoms in schizophrenia: a neuropsychological study.

Using neurocognitive testing, the present study assessed whether obsessions and compulsions could represent a distinct cluster of symptoms in schizophrenia. We formulated our hypothesis based on data from nonschizophrenic patients, expecting to find that schizophrenic patients with obsessive-compulsive (OC) symptoms would experience more difficulties in the same cognitive areas as nonschizophrenic patients with obsessive-compulsive disorder (OCD). Patients had separate psychiatric and cognitive evaluations. The OC and non-OC schizophrenic subjects did not differ significantly on the positive and negative symptom scores. However, compared with non-OC schizophrenic patients, those with OC symptoms performed worse on cognitive areas thought to be impaired (i.e., visual-spatial skills, delayed nonverbal memory, and cognitive shifting abilities). In addition, the severity of OC scores correlated with poor performance in these areas of cognition. Our results support our hypothesis, specifically that OC symptoms may constitute a distinct cluster separate from psychosis in schizophrenia and raise the possibility of a distinct subtype of schizophrenia. The theoretical and clinical implications of these findings are discussed.

Regional cerebral blood flow during the Wisconsin Card Sort Test in schizotypal personality disorder.

Regional cerebral blood flow (rCBF) was measured by single photon emission computed tomography in 10 patients with schizotypal personality disorder (SPD) and nine age- and sex-matched normal volunteers. Subjects performed both the Wisconsin Card Sort Test (WCST) and a control task, the Symbol Matching Test (SMT). Four-way analyses of variance were performed to assess relative rCBF of the prefrontal cortex and of the medial temporal region. Normal volunteers showed more marked activation in the precentral gyrus, while SPD patients showed greater activation in the middle frontal gyrus. Relative flow in the left prefrontal cortex was correlated with better WCST performance in normal volunteers. SPD patients, however, showed no such correlations in the left prefrontal cortex, but demonstrated correlations of good and bad performance with CBF in the right middle and inferior frontal gyrus, respectively. Thus, at least some SPD patients demonstrate abnormal patterns of prefrontal activation, perhaps as a compensation for dysfunction in other regions.

Regional cerebral blood flow changes associated with risperidone treatment in elderly schizophrenia patients: a pilot study.

Although there is evidence that some schizophrenia patients may have altered regional cerebral blood flow patterns, few studies have addressed the relationship between cortical activity and changes in psychiatric symptoms following treatment, particularly in the elderly. We took advantage of an existing safety and tolerance study of risperidone in the elderly and examined the possible relationship between changes in psychiatric symptoms following risperidone and changes in relative cortical perfusion in a group of 6 elderly schizophrenia patients. All subjects were at least 65 years old and diagnosed with schizophrenia according to DSM-III-R criteria. The patients were assessed using the Positive and Negative Syndrome Scale for Schizophrenia (PANSS) and Mini-Mental Status Examination (MMSE) and had single photon emission computed tomography (SPECT) studies before and at least 3 weeks after change of their previous neuroleptic to risperidone. The frontal/total cortex and temporal/total cortex counts in the slice ratios, and 99mTechnitium-hexamethylpropylene amine oxime (99mTc-HMPAO) percentage uptake in the whole cortical area in the slice were used for data analysis. With risperidone, patients (age 66-81) scored better on the PANSS, particularly in the positive symptom subtests. The changes in positive symptom scores correlated directly with those in frontal and temporal relative activity and 99mTc-HMPAO percentage uptake in the whole cortical area in the slice. Our findings suggest that the improvement in psychotic symptoms after risperidone is associated with a decrease in frontal and temporal activity and a reduction in 99mTc-HMPAO percentage uptake in the entire cortical area in the slice and agree with data from younger populations. Comparative studies assessing the therapeutic impact of neuroleptics on cortical activity in different age groups could be helpful in examining both the mechanisms of action of various drugs and the links between symptoms and specific brain areas.

Lateral ventricular enlargement in schizotypal personality disorder.

Although an increase in the ratio of ventricular space to brain (ventricle-brain ratio), VBR) on computed tomography (CT) has been among the most robust findings in chronic schizophrenia, VBR has not been investigated in a large, well-characterized clinical population of patients with schizotypal personality disorder (SPD), a clinical entity with a phenomenologic, gentle biological, and treatment response relationship to chronic schizophrenia. Accordingly, CT scans were obtained in 36 male SPD patients, 23 males with other personality disorders, 133 male schizophrenic patients, and 42 male normal volunteers. The mean body of the lateral VBR was significantly greater in the SPD patients than in the patients with other personality disorders. The VBR of the SPD patients did not differ significantly from either that of the normal volunteers or the schizophrenic patients but was intermediate between the two groups. There were no correlations with either psychotic-like or deficit-related symptoms of SPD in either the SPD or total personality disorder cohorts. SPD patients, like schizophrenic patients, may have increased VBRs compared wit patients with other personality disorders; their VBRs fall between the means of schizophrenic patients and normal control subjects.

Treatment of obsessive-compulsive symptoms in schizophrenic patients with clomipramine.

Recent studies show that obsessive-compulsive symptoms may occur in many patients with schizophrenia and may predict a poor prognosis. Pilot studies have shown that some schizophrenic patients may improve if a serotonin reuptake blocker is added to their neuroleptic. We have performed a pilot, double-blind, crossover study of clomipramine (CMI) or placebo, added to maintenance psychotropic medication. Six schizophrenic patients with obsessive-compulsive symptoms were studied in a double-blind CMI versus placebo crossover protocol. The patients met DSM-III-R criteria for chronic schizophrenia, experienced obsessive-compulsive symptoms, and had been previously stabilized on their psychiatric medication. The patients were rated at baseline and longitudinally through the study with the Positive and Negative Symptom Scale for Schizophrenia (PANSS) and the Yale Brown Obsessive-Compulsive Scale (YBOCS). An analysis of covariance was used to compare the drug versus placebo effect at the final visit with the baseline rating as a covariate. Ratings on both the YBOCS and the PANSS showed that patients improved significantly more on CMI than on placebo. No patients experienced an exacerbation of psychotic symptoms. Preliminary findings from this double-blind, crossover, pilot study of CMI and placebo, designed to assess the effect of CMI in the treatment of schizophrenic patients with obsessive symptoms, suggest that CMI is superior to placebo in the treatment of obsessions and compulsions and improves overall schizophrenic symptoms. Further studies with larger samples and longer follow-up period are necessary to confirm these preliminary findings.

Severity of symptoms in chronically institutionalized geriatric schizophrenic patients.

OBJECTIVE: The goal of this study was to characterize the symptoms of geriatric, chronically ill, institutionalized schizophrenic patients and investigate age-related differences in schizophrenic symptoms and cognitive performance from early adulthood to late senescence. METHOD: The Positive and Negative Syndrome Scale and the Mini-Mental State examination were used to assess the schizophrenic symptoms and cognitive performance, respectively, of 393 institutionalized schizophrenic patients stratified into seven groups designated by 10-year age intervals from 25 years to over 85 years. RESULTS: In the comparisons of the seven age groups, significant differences between groups in positive and negative subscale scores on the Positive and Negative Syndrome Scale and in Mini-Mental State scores were revealed. Significant correlations between Mini-Mental State scores and Positive and Negative Syndrome Scale negative symptom scores, but not positive symptom scores, were found for all age groups, except for the youngest patients studied. Current treatment with neuroleptics and prior treatment with ECT, insulin coma, or leukotomy could not account for the poor cognitive performance of the older schizophrenic patients. CONCLUSIONS: The older schizophrenic patients continued to experience psychotic and nonpsychotic symptoms in senescence. Their positive symptoms were moderately less severe and their negative symptoms and cognitive impairment were significantly more severe than those of the younger patients. Somatic treatment appeared not to be responsible for the severe cognitive impairment and negative symptoms of the older patients. These data are relevant to chronically hospitalized geriatric schizophrenic patients but not necessarily to all geriatric schizophrenic patients.

Lateralized visual-field inattention in schizophrenia.

Numerous studies have shown impaired verbal functioning in schizophrenic patients as compared with normals. The verbal deficits are generally attributed to damage of the left cerebral hemisphere. This attribution is based on literature which suggests that verbal processing is primarily mediated by the left hemisphere in right-handed humans. This study explored left-hemispheric integrity directly by assessing sustained attention in both the left and right hemispheres of 40 schizophrenic patients with the Weintraub Cancellation Tasks. Patients made significantly more errors of omission on the right visual field than on the left. These results are consistent with cognitive research in schizophrenia by demonstrating selective left-hemispheric impairment relative to right-hemispheric functioning.

Cortical cholinergic markers in schizophrenia.

Cortical cholinergic deficits have been implicated in the cognitive deficits produced by a variety of neurodegenerative diseases including Alzheimer's disease (AD). Recent studies have suggested that many of the chronically institutionalized geriatric schizophrenic patients are also cognitively impaired. In this postmortem study we compared cholinergic marker activity in six different cortical regions derived from elderly controls, chronically institutionalized geriatric schizophrenic patients, and AD patients. All of the Alzheimer's disease cases met neuropathological criteria for AD, while none of the schizophrenic cases met criteria for AD. Cholinergic marker activity (choline acetyltransferase and acetylcholinesterase) was significantly diminished in the AD cohort but not in the schizophrenic cohort. Additionally, cortical choline acetyltransferase activity was significantly and negatively correlated with Clinical Dementia Rating scores (CDR), whereas no such correlations were evident in the schizophrenic cohort. These results suggest that cognitive deficits in geriatric schizophrenics are not due to diminished cortical cholinergic activity.

Alzheimer's-disease-related protein in geriatric schizophrenic patients with cognitive impairment.

The authors compared Alz-50 immunoreactivity in the brain tissue of nine cognitively impaired elderly schizophrenic patients and 13 elderly comparison subjects, both without neuritic plaques or neurofibrillary tangles, and 13 patients with Alzheimer's disease. Alz-50 reactivity was absent in the schizophrenic patients, indicating that geriatric, cognitively impaired patients are unlikely to display the pathology of Alzheimer's disease.

Magnetic resonance abnormalities in HIV infection: a study in the drug-user risk group.

Cognitive impairment is a frequent complication of advanced human immunodeficiency virus-1 (HIV-1) infection. However, structural imaging of the brain has not revealed abnormalities that precede the onset of clinical abnormalities. Cranial magnetic resonance (MR) studies were performed in 28 male subjects with intravenous drug use histories; nine were HIV-1 seronegative, 11 were HIV-1 seropositive but asymptomatic, and eight were seropositive and met symptomatic criteria for acquired immune deficiency syndrome (AIDS). Cortical atrophy, but not the degree of ventricular enlargement or signal abnormalities, was increased in the seropositive group compared with the seronegative group and also differed between asymptomatic seropositive and seronegative patients. An increased level of cortical atrophy may reflect the early impact of HIV-1 infection on the brain.

Severe cognitive impairment in elderly schizophrenic patients: a clinicopathological study.

The severe cognitive impairment that affects many of the elderly schizophrenic patients could represent the outcome of schizophrenia in old age for the very severe and chronically ill patients or may be the result of lengthy institutionalization and somatic treatment. Alternatively, it could be due to the presence of concurrent dementing disorders, such as Alzheimer's disease (AD) or multi-infarct dementia. Using an identical neuropathological protocol, brain specimens from schizophrenic patients who showed evidence of severe cognitive impairment were compared with 12 age-matched control cases and the same number of age-matched cases of neuropathologically confirmed patients with AD. Despite their relatively advanced age (mean age 77.1 years +/- 2.8), none of the schizophrenia cases showed sufficient degree of senile plaques and neurofibrillary tangle formations to confirm a diagnosis of AD. Other neurodegenerative disorders associated with dementia were also not identified. These studies suggest that alternative explanations need to be sought for the severe cognitive impairment commonly encountered in elderly schizophrenic patients.