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Biomedical subjects

J A Sweeney

Publications and source records attributed to J A Sweeney.

At least 19 recordsLinked to original sources

Neuroendocrine and behavioral responses to challenge with the indirect serotonin agonist dl-fenfluramine in adults with obsessive-compulsive disorder.

Neuroendocrine and behavioral responses to a single 60-mg oral dose of the indirect serotonin agonist dl-fenfluramine were assessed in unmedicated adults with obsessive-compulsive disorder (OCD) and neuroendocrine results contrasted with those in normal control subjects. Net fenfluramine-induced prolactin release did not differ significantly between OCD patients and normal controls. Prolactin responses in the OCD group were not significantly correlated with baseline Yale-Brown Obsessive Compulsive Scale scores for either obsessions or compulsions, but were positively correlated with the baseline Hamilton Depression Scale score and Hamilton Anxiety Scale score. No clear difference in the severity of patients' obsessions or compulsions was found following challenge with fenfluramine versus placebo. Although the present study does not demonstrate a serotonergic abnormality in OCD, this may be more a reflection of limitations of the test procedures than evidence that central nervous system (CNS) serotonergic function is normal in the disorder.

Adult

Pursuit eye movement dysfunction in obsessive-compulsive disorder.

Disturbances in neural circuitry including the basal ganglia and prefrontal cortex have been hypothesized to be a cause of obsessive-compulsive disorder (OCD). Because eye movements are often impaired in neurologic diseases affecting these brain areas, oculomotor functioning was assessed in 17 unmedicated patients with OCD and in 25 normal controls. As compared with control subjects, patients with OCD demonstrated low-gain (slow) pursuit eye movements and an increased frequency of square wave jerk intrusions, but no increase in anticipatory saccades. In addition, several OCD patients showed an unusual pattern of intrusive, brief epochs of high-gain (fast) pursuit lasting on the order of 50 to 130 msec. These epochs of fast pursuit moved the eyes ahead of the target being tracked, and were terminated by corrective reversal saccades. Studies of eye movement abnormalities may provide an informative neurophysiologic approach for studying disturbances in basal ganglia and frontal cortical function that have been observed in functional neuroimaging and neuropsychological studies of OCD.

Adult

Smooth-pursuit eye movement dysfunction and liability for schizophrenia: implications for genetic modeling.

Forty-one nonpsychiatric subjects, 38 probands with schizophrenia, and 99 of their relatives were studied. Oculomotor functioning was bimodally distributed for probands and relatives. Oculomotor dysfunction was not present in all families with a schizophrenic proband. In those families in which it was present, there were significant phenotypic correlations between oculomotor functioning and schizophrenia-related characteristics. The patterns of familial resemblance in the families in whom oculomotor dysfunction was present were consistent with nonadditive genetic variance contributing both to oculomotor dysfunction and to the relationship between oculomotor dysfunction and clinical symptoms. These results suggest that schizophrenia may be etiologically heterogeneous and that oculomotor dysfunction may help to identify nonadditive genetic variance for this disorder.

Adult

Neuropsychological and eye movement abnormalities in first-episode and chronic schizophrenia.

It is well known that neurobehavioral deficits are associated with schizophrenia. Little is known, however, about whether these disturbances becomes more severe over the course of the illness. In the present study, 101 patients with schizophrenia, of whom 45 were first-episode cases, performed pursuit eye tracking tasks. A subset of 60 of these patients, including 27 first-episode cases, were administered a battery of neuropsychological tests. Patients with a history of prior psychotic episodes demonstrated more severe pursuit eye movement dysfunction than first-episode patients and more severe disturbances on neuropsychological tests sensitive to prefrontal and left temporal cortical dysfunction. Longitudinal studies of patients ascertained close to the point of illness onset are needed to determine whether these findings reflect a progressive deterioration in neurobehavioral functioning over the course of schizophrenia.

Adult

Premorbid and onset features of first-episode schizophrenia.

Most descriptive studies of the psychopathology of schizophrenia have focused on the period following illness onset. Little attention has been paid to the assessment of psychopathology before onset of psychotic symptoms. In this study, 71 first-hospitalization patients diagnosed with schizophrenia, schizoaffective, or schizophreniform disorder using DSM-III-R criteria were assessed on measures of premorbid adjustment, clinical history, and presenting symptomatology. A pattern of progressive decline was characteristic of 21 percent of the cases--primarily males with a long-term history of psychotic symptoms before first hospitalization and a trend for more severe negative symptoms at hospital admission. Patients who had a stable pattern of good premorbid adjustment experienced symptom onset and first hospitalization at a later age than those with a chronically poor premorbid adjustment. Time from onset of first psychotic symptom to first hospitalization varied from less than 1 month to over 20 years and was not associated with symptom severity or age of first psychotic symptoms. Systematic characterization of the earliest manifestations of schizophrenia may be important in identifying subgroups of patients with a similar course of illness, and may ultimately facilitate diagnosis, treatment, and understanding of the pathophysiology of schizophrenia.

Adult

Clinical correlates of cerebral ventricular enlargement in schizophrenia. Further evidence for frontal lobe disease.

Numerous studies have shown evidence of cerebral ventricular enlargement in schizophrenia and its relationship to severity of clinical symptoms and psychosocial dysfunction. In this large prospective study, 88 noninstitutionalized DSM-III-R schizophrenic patients were administered a CT scan and rated for positive and negative symptomatology and premorbid adjustment. The CT scans from 14 healthy controls were used for comparison of cerebral ventricular measures. Patients had an enlarged ventricle to brain ratio of the anterior portion of the lateral ventricles, the frontal horns, compared with controls. Patients with larger frontal horns had more severe negative symptoms and poorer premorbid childhood adjustment. The area of the main body of the cerebral lateral ventricles, though not elevated in patients, was correlated with the total number of prior hospitalizations. These results support the hypothesis of a structural and functional "frontal" deficit in schizophrenia.

Adolescent

Bizarre delusions and DSM-III-R schizophrenia.

OBJECTIVE: Bizarre delusions are assigned greater weight relative to other delusions in the DSM-III-R diagnosis of schizophrenia. The decision to emphasize bizarre delusions was based largely on historical tradition rather than empirical evidence. This study examined 1) the extent to which a history of bizarre delusions contributes to the diagnosis of schizophrenia and 2) whether schizophrenic patients with bizarre delusions constitute a clinically distinguishable subgroup. METHOD: Two hundred fourteen consecutively admitted psychotic inpatients were assessed for bizarre delusions according to the DSM-III-R criteria. Clinical and demographic correlates of bizarre delusions were examined in subsets of patients diagnosed as schizophrenic according to DSM-III-R who also received CT scans and neuropsychological testing. RESULTS: With the base prevalence rate for schizophrenia of 0.71, bizarre delusions had a sensitivity of 0.79, a specificity of 0.56, and a positive predictive power of 0.82 for the diagnosis of schizophrenia (N = 152) relative to other psychotic disorders (N = 62). Clinical, neurobehavioral, CT scan, and premorbid adjustment data on the schizophrenic patients indicated that beyond manifesting more severe positive symptoms, patients with bizarre delusions did not otherwise constitute a clinically distinguishable subgroup. CONCLUSIONS: The data suggest that criterion A for the diagnosis of schizophrenia in DSM-IV could be improved by removing the special emphasis that was placed on bizarre delusions in DSM-III-R.

Adolescent

Evaluation of the stability of neuropsychological functioning after acute episodes of schizophrenia: one-year followup study.

Few studies have evaluated the longitudinal stability of neuropsychological deficits in schizophrenia. In the present study, 39 inpatients with DSM-III-R schizophrenia were administered a comprehensive battery of neuropsychological tests after achieving sufficient clinical recovery to warrant discharge, and again 1 year after the first assessment during a nonacute period. Significant improvement in neuropsychological functioning from the first to the second assessment was observed on several tasks, including the following: Trails A and B, Digit Symbol, Judgment of Line Orientation, recognition memory on the Rey Auditory Verbal Learning Test, the Wisconsin Card Sort, and Finger Tapping. These improvements were unrelated to treatment history, and were similar in first episode and chronic cases. For many patients, the improvement in functioning brought test performance into line with normative scores from test standardization samples. These results indicate that considerable improvement in neuropsychological functioning can occur in schizophrenic patients over the months following an acute episode of illness, and that recovery of cognitive functioning can occur after substantial clinical recovery from an acute episode of illness has already been achieved.

Adolescent

Relationships between medication treatments and neuropsychological test performance in schizophrenia.

Few investigations have assessed the neuropsychological effects of psychotropic medications on schizophrenic patients. In this study, 44 clinically stable schizophrenic inpatients were administered a battery of neuropsychological tests, and their performance was correlated with dosage of neuroleptic medication and benztropine. Neuroleptic dose was correlated with poorer performance on tests of psychomotor speed and attention, and with the number of perserverative errors on the Wisconsin Card Sort. Anticholinergic dose was associated with poorer verbal learning, verbal fluency, and motor speed. Both medication dosages were associated with poorer verbal recognition memory, but this association was strongly influenced by the performance of individuals on the highest medication doses. The findings, which were independent of clinical state and intelligence, indicate that higher doses of neuroleptic and anticholinergic medications are associated with poorer neuropsychological functioning in schizophrenia.

Adult

Phenotypic correlations between oculomotor functioning and schizophrenia-related characteristics in relatives of schizophrenic probands.

Abnormalities of visual pursuit tracking are frequent in the first-degree relatives of probands with schizophrenia. The relationship between oculomotor abnormalities and schizophrenia-related characteristics in those family members, however, has received little attention. Fifty-three first-degree relatives of 24 probands with schizophrenia were evaluated for the presence of schizophrenia-related characteristics using both interview (Schedule for Schizotypal Personalities) and questionnaire (Chapman scales). The family members also had their eye movements recorded during pursuit tracking tasks and scored for gain in both the frequency and time domains, and saccadic intrusions. Social-interpersonal schizophrenia-related features were significantly related to both time- and frequency-domain gain calculations. It appears that abnormalities in the smooth-pursuit oculomotor system may be associated with symptoms conjectured to be most closely related to a genetic diathesis for schizophrenia. These findings provide further evidence that oculomotor abnormalities may be related to risk for this disorder.

Adult

Pursuit eye movement dysfunction in HIV-1 seropositive individuals.

Studies of smooth pursuit eye movements were conducted in 30 ambulatory drug-free HIV-1 seropositive patients who did not yet manifest marked clinical signs of the AIDS Dementia Complex. Seropositive patients demonstrated disturbances in pursuit eye movements that were correlated with extent of immunosuppression, with impairments on neuropsychological tests of fine motor control/speed, and with independent clinical staging of the AIDS Dementia Complex. The results provide quantitative evidence that oculomotor disturbances are present in HIV-1 seropositive individuals before the manifestation of marked AIDS Dementia Complex. For this reason, and because more severe eye movement impairments have been observed in patients with AIDS, quantitative eye movement studies may provide a useful neurobehavioral procedure for characterizing and monitoring progression of CNS involvement associated with HIV-1 infection from early in its course.

Adult

Statistical issues in the identification of risk factors for suicidal behavior: the application of survival analysis.

Studies of suicide risk factors generally examine suicidal behavior as a dichotomous outcome. Survival analytic techniques are discussed in which the time until a suicide attempt from a specific point, such as prior attempt or onset of illness, is also examined. These procedures can incorporate information on those lost to followup or "censored." One survival analytic technique, Cox's proportional hazards model, is a particularly informative statistical technique for the study of suicidal risk factors because several covariates can be incorporated. Illustrative analyses estimate the significance of different risk factors, and demonstrate that there is a 32% increase in the relative risk of a suicide attempt associated with each prior attempt.

Adult

Pursuit gain and saccadic intrusions in first-degree relatives of probands with schizophrenia.

Oculomotor functioning of 26 probands with schizophrenia, 12 spectrum and 46 nonspectrum first-degree relatives, and 38 nonpsychiatric control subjects was evaluated. Spectrum relatives had more anticipatory saccades (ASs) and lower pursuit gain than nonspectrum relatives, who had more ASs and lower pursuit gain than control subjects. Probands also had lower pursuit gain than nonspectrum relatives and control subjects but did not differ from other groups on AS frequency. Control subjects had more globally accurate pursuit tracking (root mean square [RMS] error deviation) than both relative groups, whereas probands had the poorest RMS scores. Square wave jerk frequency did not differentiate the groups. Attention enhancement affected the frequency of ASs but did not affect either the other intrusive saccadic event or RMS scores. These results offer evidence that eye-movement dysfunction may serve as a biological marker for schizophrenia.

Adolescent

Is eye movement dysfunction a biological marker for schizophrenia? A methodological review.

There is a high prevalence of eye movement dysfunction (EMD) in persons with schizophrenia and their first-degree relatives. Studies addressing the prevalence, stability, familial transmission, and psychological correlates of EMD in persons from both psychiatric and general populations offer suggestive evidence that this abnormality may serve as a biological marker for schizophrenia. Although these findings are promising, their significance for elucidating the diagnostic bandwidth, pathophysiology, and genetics of this disorder remains to be determined. More precise characterization of ocular motility, perhaps when used in conjunction with global measures of pursuit adequacy, may be essential for clarifying the pathophysiological and genetic significance of EMD for schizophrenia. Recent research efforts are beginning to identify particular abnormalities that could serve as more specific biological markers for schizophrenia.

Eye Movements

Endoscopy assessment tool--a new approach.

Endoscopy outpatient assessment should be simple, yet comprehensive. Assessment is done to identify nursing care problems in order to deliver appropriate care. Four weaknesses are commonly found with outpatient assessment tools: assessment criteria are not based on Standards of Care, abnormal findings are not easily identifiable, nursing care problems are not stated, and there is no stated plan of care. The purpose of this paper is to introduce a new concept for the GI outpatient assessment. In the proposed concept, the "traditional" assessment is merged with a nursing care plan to produce a comprehensive assessment tool. Assessment criteria are based on predetermined Standards of Care. The assessment analysis is stated via the same assessment tool as a nursing problem, and the care plan interventions are noted and based on nursing care problems.

Ambulatory Care

A controlled study of the antidepressant efficacy and side effects of (-)-deprenyl. A selective monoamine oxidase inhibitor.

Monoamine oxidase (MAO) inhibitors are effective antidepressants whose use is limited because of unwanted side effects and the possibility of a tyramine-induced hypertensive crisis (cheese reaction). (-)-Deprenyl (the official nonproprietary name for this substance is selegiline), a selective MAO type B inhibitor, may be safer and have fewer side effects, but its antidepressant efficacy is uncertain. A double-blind placebo-controlled study was carried out in depressed outpatients who were treated with (-)-deprenyl in an MAO type B selective dose range and at a higher nonselective dose range. (-)-Deprenyl did not have a statistically significant antidepressant effect after three weeks of treatment at doses of 10 mg/d. However, after six weeks and at higher doses (averaging about 30 mg/d for the second three weeks), (-)-deprenyl was superior to placebo in antidepressant effect with a positive response rate of 50% vs 13.6% and with a 41% reduction in the Hamilton Depression Rating Scale mean score vs 10% in the placebo-treated group. No hypertensive crises were seen. The rate of occurrence of side effects with (-)-deprenyl was no greater than with placebo. It was concluded that (-)-deprenyl is an effective antidepressant in a dose range where it is distinguished by the absence of many of the side effects typical of nonselective MAO inhibitors.

Adult

Serotonergic responsivity in male young adults with autistic disorder. Results of a pilot study.

Altered serotonergic function has been postulated to exist in autistic disorder. Central serotonergic responsivity was assessed with a neuroendocrine challenge test in seven male young adults with autistic disorder and in seven age- and gender-matched healthy controls. Binding indexes and physiologic responsivity of the platelet serotonin-2 (5-HT2) receptor complex were also measured, as was whole-blood serotonin content. Compared with controls, autistic subjects had substantially blunted prolactin release in response to a 60-mg oral dose of fenfluramine hydrochloride, an indirect serotonin agonist [corrected]. Furthermore, the magnitude of serotonin-amplified platelet aggregation, mediated by the platelet 5-HT2 receptor complex, was reduced in the autistic group, as was the mean number of platelet 5-HT2 receptor sites. Among autistic subjects, fenfluramine-induced prolactin release correlated positively with the serotonin-amplified platelet aggregation response and negatively with whole-blood serotonin content. The results of the present study are compatible with the hypothesis that central serotonergic responsivity is decreased in male autistic young adults. Correlations between central and peripheral serotonergic measures in autistic subjects suggest that systemic alterations in serotonergic function may occur in autism.

Adult

Assessment of cognitive functioning in poly-substance abusers.

Neuropsychological deficits of memory and spatial perception have been associated with substance abuse. The present study assessed the degree to which verbal abstraction is impaired in substance abusers because this function typically is reduced in diffuse cerebral disorders. Test scores of 100 consecutively admitted substance-abusing patients indicated that performance on the Similarities test of the WAIS was actually higher than Vocabulary scores. This finding was replicated with the WAIS-R on a second sample of 100 patients who demonstrated impaired memory and psychomotor speed. These findings indicated that verbal abstraction was unimpaired in two large samples of poly-substance abusers. Further, the superiority of Similarities over Vocabulary scores suggests that in poly-substance abusers, Similarities scores may be a better index of premorbid intellectual competence than the more typically used Vocabulary scores.

Adult