The CATIE schizophrenia effectiveness trial.
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Antipsychotic Agents↗
Biomedical subjects
H A Nasrallah
Publications and source records attributed to H A Nasrallah.
Iatrogenic disorders associated with conventional vs. atypical antipsychotics.
Pharmacotherapy is an indispensable component of the management of schizophrenia and related psychotic disorders. Antipsychotic drugs are used for their efficacy in controlling the symptoms of psychosis. However, the side effects of antipsychotic drugs can have a deleterious impact on the course of the illness by inducing iatrogenic symptoms of various severity. The side effects of first-generation or conventional antipsychotic drug were often so intolerable to patients with schizophrenia that their compliance was consistently poor, leading to frequent relapse, chronicity, and impaired functioning. The second-generation (atypical) antipsychotics, introduced 40 years after the advent of the older-generation, are proving to have better outcomes in psychosis not only because of broader symptom efficacy but also because their side-effect profile is more tolerable, leading to higher compliance and fewer relapses. The authors review the side effects of the old and the new antipsychotics and conclude that the improved tolerability of the new antipsychotics is associated with greater effectiveness, not just efficacy. Differences in tolerability among the new antipsychotics are described.
Antipsychotic Agents↗
Neuropsychological correlates of negative, disorganized and psychotic symptoms in schizophrenia.
Recent studies suggest that three dimensions (negative, disorganized and psychotic) categorize schizophrenic symptoms. A developing literature indicates distinct cerebral correlates of each symptom cluster, but few investigations have determined their neuropsychological correlates. In the present study, the Schedules of Negative and Positive Symptoms measured symptom severity in 62 schizophrenics, and a subsequent principal components analysis revealed three symptom dimensions. Factor scores, age and parental socio-economic status were simultaneously entered into regression equations to explain variance across a broad neuropsychological test battery. Negative symptoms were associated with deficits involving intelligence, executive function, memory, sustained-attention and sensory-motor function, whereas disorganized symptoms correlated with decreased intelligence, attention-span and sensory-motor function. Psychotic symptoms were unrelated to deficits. These data are consistent with hypotheses that these three symptom dimensions have distinct neurobehavioral correlates.
Adolescent↗
Clinical correlates of response to valproate in geriatric inpatients.
The efficacy of valproate for the management of adults with bipolar disorder has been repeatedly demonstrated in several studies. Patients with mixed states, rapid cycling, and EEG abnormalities have been shown to respond favorably to valproate. Valproate is also being increasingly used in disorders with aggressive or agitated features, such as the behavioral disorders of dementia; yet, few studies have documented the utility of valproate in geriatric patients. The need to document safe and effective pharmacologic agents to treat geriatric mood and behavioral disorders continues to increase with the growing elderly population. We conducted a retrospective study of the use of valproate in patients consecutively hospitalized over a 5-year period on a psychiatric unit. Thirty-nine patients over age 60 were identified and then categorized into non-, partial, and full responders based on Clinical Global Impression ratings. Information on diagnosis, age, valproate dose and serum concentration, psychiatric symptoms, medical comorbidity, concurrent psychotropic medications, and side effects was collected. Results suggest that responders to valproate (full or partial) over the age of 60 years were more likely to be female, younger, carry a diagnosis of bipolar disorder, and achieve higher serum valproate concentrations. Full responders had fewer psychotic symptoms but usually displayed manic symptoms. The date of this study suggests the need for controlled clinical trials to clarify the utility and clinical predictors of response to valproate in the geriatric population.
Age Factors↗
Neurobiology and neuroplasticity in schizophrenia. Continuity across the life cycle.
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Adolescent↗
The volume of the entorhinal cortex in schizophrenia: a controlled MRI study.
1. The entorhinal cortex (EC), part of the limbic temporal lobe, is a critical link between the cerebral cortex and the hippocampus, and is considered one of the most important cortical "association" areas. Several postmortem abnormalities in the EC have been reported. 2. Here, the authors report the first in vivo study of the volume of the EC in schizophrenia using magnetic resonance imaging (MRI) scans. 3. The authors compared 57 schizophrenic patients and 35 healthy controls. No overall difference in the mean EC volume was found between controls and schizophrenic patients, but there was a strong trend (p = .078) for the schizophrenic females to have a large mean EC than control females and for the early onset schizophrenia group to have a smaller (EC (p = .07) than late onset schizophrenia subjects. 4. The implications of the findings are discussed.
Adolescent↗
Postpartum mood disorders: clinical perspectives.
Mood disorders are common in women. A prepregnancy personal history of mood disorder (bipolar or major depression), premenstrual syndrome, or (possibly) postpartum blues places a woman at high risk for a postpartum exacerbation of symptoms. Untreated or unrecognized postpartum mood disorders can lead to serious psychologic and social consequences, in some cases even leading to suicide or infanticide. Women at risk for postpartum mood disorders need to be referred for psychiatric consultation before pregnancy and parturition. Informed, professional collaboration offers the best opportunities for prevention, as well as the earliest recognition and treatment of emergent symptoms.
Affective Disorders, Psychotic↗
Cognitive deficits distinguish patients with adolescent- and adult-onset schizophrenia.
Recent studies have shown that patients with schizophrenia who have an adolescent-symptom onset (before age 21) have a worse clinical course and greater frequency of cerebral abnormalities than those with an adult-onset (after age 25). However, little is known about the neuropsychological functioning of these groups. A comprehensive neuropsychological examination was administered to groups of patients with schizophrenia with either an adolescent- or adult symptom-onset and a healthy control group. The adolescent-onset group performed worse than the adult-onset and control groups, particularly on measures of memory and executive function. The adult-onset group also performed worse than the controls, but to a lesser extent than did the adolescent-onset group. Results are discussed with reference to hypotheses that adolescent-onset schizophrenia represents a distinct neurodevelopmental disease entity.
Adolescent↗
Evoked potentials in subjects at risk for Alzheimer's disease.
Evoked potential (EP) changes accompanying dementing processes have been documented in a number of studies. However, EPs have not been studied in subjects who are at heightened risk for the development of Alzheimer's Disease (AD). Nineteen volunteers with no immediate family members with a history of AD and 33 healthy subjects with at least one first-degree relative with AD were studied. Of the 33 subjects with a positive family history of AD, the illness of the sick relative was classified as possible AD in 10 subjects, probable AD in 17 subjects, and definite (autopsy-proven) AD in 6 subjects. Mid-latency evoked potentials (P50, N100, and P200) and P300 event-related potentials were recorded in an oddball paradigm. The amplitudes of the P50 responses to the frequent stimuli and of the P300 responses were significantly higher in the subjects whose relatives had definite AD as compared with the other three groups. The amplitude of the N100 component was also larger in the same group, but the difference was only statistically significant from the group of healthy volunteers without a family history of AD. A process of increased sensitivity to incoming stimuli may be reflected in the increased P50, N100, and P300 amplitudes in the subjects at increased risk for developing AD.
Alzheimer Disease↗
The P50 evoked potential component and mismatch detection in normal volunteers: implications for the study of sensory gating.
Sensory gating is a complex, multistage, multifaceted physiological function believed to be protecting higher cortical centers from being flooded with incoming irrelevant sensory stimuli. Failure of such mechanisms is hypothesized as one of the mechanisms underlying the development of psychotic states. Attenuation of the amplitude of the P50 evoked potential component with stimulus repetition is widely used to study sensory gating. In the current study, we investigated the responsiveness of the P50 component to changes in the physical characteristics of ongoing trains of auditory stimuli. Forty normal volunteers were studied in a modified oddball paradigm. At all cerebral locations studied, P50 amplitudes were higher in response to infrequent stimuli. We postulate that the increase in P50 amplitude reflects the system's recognition of novel stimuli or "gating in" of sensory input. The ratio of the amplitude of the responses to the infrequent stimuli to those of the frequent stimuli was significantly higher for the posterior temporal regions. This finding provides further evidence that the temporal lobes may be significantly involved in sensory gating processes. Although this study only included normal subjects, the data generated contribute to the understanding of sensory gating mechanisms that may be relevant to psychotic states.
Adolescent↗
Brain and CSF volume differences in schizophrenic subtypes.
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Adult↗
Neuropsychological performance and CD4 levels in HIV-1 asymptomatic infection.
The performance of 68 HIV-1 seropositive asymptomatic (HIV+) subjects stratified on CD4 levels were compared with 82 HIV-1 seronegative (HIV-) subjects on a battery of neuropsychological, mood state, and perceived health status measures. The neuropsychological test battery included measures of attention, reaction time, memory, intellectual ability, psychomotor speed, frontal lobe or "executive" function, and decision time. None of the HIV+ subjects were taking antiviral agents. The groups did not differ for age, mood state, or WAIS-R Verbal and Performance IQ scores. Due to group differences for education and weekly ethanol consumption, both variables were used as covariates in multivariate analyses of variance. Relatively few differences were observed between subgroups of HIV+ patients or between these subgroups and control subjects. These data suggest that factors other than absolute levels of immunosuppression as expressed by CD4 levels alone, appear to be responsible for the deficits observed in HIV+ asymptomatic patients.
AIDS Dementia Complex↗
Self-report of symptoms and neuropsychological performance in asymptomatic HIV-positive individuals.
This study examined the relationship between subjective complaints and neuropsychological performance in 133 HIV-positive asymptomatic and 80 HIV-negative gay or bisexual men. Presence and duration of self-reported symptoms were most strongly related to measures of information processing and reaction time. These relationships remained significant when the effect of depression was statistically controlled, and no significant relationships were found between CD4 level and either presence or duration of symptoms. These data suggest that 1) depression does not completely account for the relationship between subjective complaints and neuropsychological performance and 2) early subjective recognition of symptoms may represent a risk factor for subsequent development of neurobehavioral abnormalities.
Adult↗
Duration of illness and neuropsychological performance in asymptomatic HIV infection.
The relationship between duration of illness and neuropsychological performance was examined in 25 asymptomatic HIV-infected men with an estimated date of seroconversion. Mean duration of illness was approximately 2 years. After controlling for CD4 level at the time of neuropsychological examination, duration of illness was correlated with measures of visual attention, mental flexibility, dexterity, auditory information processing, and response fluency, as well as an overall measure of neuropsychological performance. Although these patients performed within normal limits, these data suggest that duration of infection may be related to subtle alterations in neuropsychological performance. These results are discussed with regard to possible mechanisms that implicate gradual accumulation of neurotoxins.
AIDS Dementia Complex↗
Proton magnetic resonance spectroscopy (1H MRS) of the hippocampal formation in schizophrenia: a pilot study.
BACKGROUND: Recent post-mortem and magnetic resonance imaging (MRI) studies strongly suggest a decrease in the volume of the hippocampus and other limbic temporal structures in schizophrenia. Therefore, we hypothesised that N-acetyl aspartate (NAA) which is found mainly in neurons and which can be measured by proton magnetic resonance spectroscopy (1H MRS) would be decreased in the limbic temporal region in schizophrenia. METHOD: Consenting subjects fulfilling DSM-III-R criteria for schizophrenia (n = 11) and matched healthy volunteers (n = 11) who were recruited in a tertiary university referral centre, participated in a 1H MRS brain study. Proton MRS spectra were obtained from a 12 cm3 voxel (2 x 2 x 3 cm) in the right and left hippocampus/amygdala region. A researcher blind to the source of the spectra, measured the NAA intensity in all subjects, which were then statistically compared across the two groups. RESULTS: NAA intensities were significantly reduced in the right hippocampus/amygdala region of schizophrenic patients (P = 0.038). The difference of the left side did not reach significance at the 95% confidence level. CONCLUSIONS: The findings of decreased NAA in this study suggest that there may be a decrement in neuronal number or tissue volume of the right hippocampal/amygdala region in schizophrenia. Biochemical alterations in the metabolism of NAA in schizophrenia may be an alternative explanation. The findings are consistent with other types of post-mortem and in vivo evidence for hypoplasia of the limbic temporal structures in schizophrenia, postulated to be of neurodevelopmental pathogenesis.
Adult↗
Cavum septum pellucidum in schizophrenia, affective disorder and healthy controls: a magnetic resonance imaging study.
Many structural brain abnormalities have been described in schizophrenia, consistent with a neurodevelopmental model for this disease. We report here a study of the cavum septum pellucidum (CSP) in schizophrenia compared to control groups, as well as the clinical correlates of this congenital anomaly in schizophrenia. We conducted a magnetic resonance imaging (MRI) study to compare rates of CSP in schizophrenia (N = 67) v. psychiatric controls (bipolar and schizoaffective, N = 60) and healthy controls (N = 37). Of the controls 18.9%, and of all psychotic subjects 18.1% had a CSP of any size and there was no difference in the frequency of large CSP among the groups. Males had higher rates of CSP than females (25% v. 9.7%, P = 0.01) in all groups. Schizophrenics had higher CSP rates than affective patients (25%, v. 10%, P = 0.02). No clinical difference was found between schizophrenics with or without CSP.
Adolescent↗
Neuropsychological performance in symptomatic and asymptomatic HIV infection.
OBJECTIVE: To examine cognitive function in patients at various stages of HIV infection, and to determine the nature and severity associated with stage of illness. DESIGN: Subjects were administered an extensive battery of neuropsychological tests. SUBJECTS: Two hundred and thirty-three HIV-1-infected homosexual/bisexual men and 77 HIV-negative control subjects who had been screened for previous neurological illness. All subjects were volunteers in a longitudinal study of neurobehavioral complications of HIV infection. RESULTS: Patients with symptomatic infection differed from controls on a large number of measures, and asymptomatic patients had a more circumscribed pattern of deficit. On a summary measure of cognitive impairment, there was a twofold increase in the prevalence of impairment in asymptomatic patients relative to controls, and a fourfold increase in symptomatic patients. Memory and dexterity problems appear to be early features of neurobehavioral dysfunction, and frontal lobe deficits were found in patients with symptomatic infection. CONCLUSION: These data indicate that there is a steady increase in the prevalence of neurobehavioral abnormalities associated with stage of infection. The pattern of abnormality also varies with disease stage.
Acquired Immunodeficiency Syndrome↗
Change in neuropsychological performance in asymptomatic HIV infection: 1-year follow-up.
OBJECTIVE: To examine the stability of cognitive function in patients with asymptomatic HIV infection. DESIGN: Previous longitudinal studies of cognitive function have focused on patients who progress in terms of disease stage. The present study avoided this potential confounding factor by including only subjects who remained in the asymptomatic stage of infection over the follow-up period. METHOD: Subjects were administered an extensive neuropsychological test battery at baseline and 1 year follow-up. Overall performance was characterized as normal or abnormal based on the performance of a well-matched HIV-negative control group. RESULTS: A significantly higher proportion of HIV-positive subjects became abnormal at the follow-up examination. Comparison of the seropositive subjects who remained normal with those who became abnormal revealed no differences at baseline on age, education, depression or CD4 levels. Subjects who became abnormal had worse performance at baseline on measures of information processing, verbal learning and memory, and reaction time. CONCLUSIONS: These data indicate that cognitive function may decline in some patients who continue to be in the asymptomatic stage of infection. Patients with a pattern of cognitive abnormalities at baseline, which includes information processing and reaction time deficits, may be at increased risk for declines in function during early stages of infection.
Adult↗