Biomedical subjects

W Perry

Publications and source records attributed to W Perry.

At least 19 recordsLinked to original sources

PubMed2002

Combined oral estradiol valerate-norethisterone treatment over 3 years in postmenopausal women: effect on lipids, coagulation factors, haematology and biochemistry.

OBJECTIVE: To determine the effect of continuous estradiol valerate 2 mg and norethisterone 0.7 mg daily as hormone replacement on lipid profiles, coagulation factors, haematology and biochemistry over 3 years. METHODS: An open label trial with 107-133 postmenopausal women assessed pre-treatment and at annual visits with extensive lipid and coagulation profiles, and observation of circulatory adverse events. Standard haematology and biochemical profiles were also analysed. Results were compared at point of entry and at 36 months. RESULTS: Total cholesterol (TC) and HDL and LDL fractions fell significantly (P=0.0001) and there was a significant decline in favourable ratios as well as a rise in VLDL mass (P=0.0001). Lipoprotein (a) (Lp(a)) decreased significantly (P=0.0053). Fibrinogen, free protein, prothrombin time and thrombin increased (P=0.0001) while platelets and KPTT were unchanged. Protein C, antithrombin III and total protein S decreased (P=0.0001) and there was a rise in the frequency of lupus anticoagulant positivity. Significant but small changes were seen in haematology and biochemical parameters although this did not raise safety issues and their clinical significance was uncertain. CONCLUSION: The direction of lipid and coagulation factors move in competing ways, emphasising the complexity of metabolic change and making interpretation of outcome for venous and arterial thrombosis or atherosclerosis difficult to predict. Eight patients developed thromboembolic or ischaemic events over the 3 year period of this study but these patients had lipid changes normally considered beneficial to cardiovascular disease and coagulation changes not thought to be associated with thromboembolism. Decrease in lipoprotein 'a' levels might be an indicator of long-term decreases in atherosclerotic events.

Adult↗

PubMed2001

Sensorimotor gating deficits in bipolar disorder patients with acute psychotic mania.

BACKGROUND: Deficits in sensorimotor gating as assessed by prepulse inhibition (PPI) and habituation of the human startle response have been noted in schizophrenia and other patients with known dysfunction in the brain substrates that regulate PPI. During acute mania, bipolar disorder (BD) and schizophrenia patients present with symptoms that are similar. To determine if these clinical similarities extend to neurophysiologic domains, PPI and startle habituation were assessed in BD patients with acute psychotic mania and compared with a sample of acutely psychotic schizophrenia patients and a normal comparison group. METHODS: Fifteen BD patients, 16 schizophrenia patients, and 17 control subjects were assessed on PPI and startle habituation. RESULTS: The BD patients had significantly lower PPI than did the control subjects in two of the three PPI conditions (60- and 120-msec interstimulus intervals) as well as less startle habituation. The BD patients did not statistically differ from the schizophrenia patients in PPI or habituation. CONCLUSIONS: These findings of sensorimotor gating deficits among bipolar disorder patients are consistent with other findings using different measures of information processing and suggest that the neurobiological substrates underlying sensorimotor gating may be dysregulated during acute manic and psychotic states.

Acute Disease↗

PubMed2001

Impact of prepulse characteristics on the detection of sensorimotor gating deficits in schizophrenia.

Schizophrenia patients have prominent deficits in information processing that can be detected by measures of prepulse inhibition (PPI) of the startle response. Deficient PPI in schizophrenia is thought to reflect a failure of brain-based information 'protective' mechanisms that normally inhibit responsivity for 30-500ms after a weak prepulse stimulus. The relationship between specific prepulse stimulus characteristics and PPI deficits in this study was examined in 31 schizophrenia patients and 34 normal comparison subjects. Schizophrenia patients had overall deficits in PPI across four conditions where the prepulse was either discrete (abrupt) or continuous (sustained) and consisted of either white noise or a pure tone. On inspection and analysis of the data, it appears that the white noise conditions, rather than tone conditions, account for the group differences. Thus, the discrete white noise prepulse was most effective in eliciting PPI deficits, resulting in a large effect size between groups (d=0.85; P<0.01). Deficits in information-protective mechanisms in schizophrenia may be differentially sensitive to specific stimulus characteristics; this observation may be relevant both to the neurobiology of information processing deficits in schizophrenia and to the methodologies for studying these deficits experimentally.

Adult↗

PubMed2001

Self-monitoring enhances Wisconsin Card Sorting Test performance in patients with schizophrenia: performance is improved by simply asking patients to verbalize their sorting strategy.

Patients with schizophrenia have Wisconsin Card Sorting Test (WCST) deficits, which are commonly interpreted as reflecting frontal cortex-based executive dysfunction. One means of assessing the refractoriness of frontal-executive impairment is to utilize a training or modification strategy to improve WCST performance. In this study, 73 patients with schizophrenia were assigned to 1 of 2 groups. Group 1 received the standard WCST instructions for 64 cards (Condition 1). For the second 64-card deck, the patients were asked to verbalize the reason that they placed the card where they did after each sort (Condition 2). Group 2 received this modified instruction 1st (Condition 1) and then the standard instructions for the second deck (Condition 2). A group of normal comparison participants was also tested using standard instructions alone. Group 2 committed significantly fewer perseverative responses than did Group 1. Furthermore, there was no significant difference between Group 2 (Condition 1) and the normal participants. Group 1's performance improved when patients were exposed to the modified instructions (Condition 2). Additionally, poor premorbid factors and disorganized symptoms were associated with decreased benefit from the modified instructions across both groups. Cumulatively, these data suggest that a simple instruction may enhance executive function and impact WCST performance in patients with schizophrenia.

Adult↗

PubMed2001

Incremental validity of the Ego Impairment Index: a re-examination of Dawes (1999).

This article examined the incremental validity of the Ego Impairment Index (EII), a Rorschach measure of cognition, perception, and reasoning. R. M. Dawes (1999) borrowed 2 previously published data sets to assess the incremental validity of the EII. Dawes determined that in order for the EII to be considered a valid measure, the overall EII score should "outperform" 2 of the variables that compose the index. Using this approach, Dawes reported that the EII had "deficient" (p = .059) incremental validity. In this study, the incremental validity of the EII was re-examined using 1 of the data sets used by R. M. Dawes (1999). Applying the same strategy as Dawes, the author tested the incremental validity of the EII in predicting positive symptoms of schizophrenia, a more appropriate and clinically relevant criterion measure of impairment. The EII significantly predicted positive symptoms (p < .005) even after the 2 EII variables selected by Dawes and the measure of social competence were 1st entered into the equation. The results suggest that the EII adds meaningful information in the assessment of thought disturbance.

Adult↗

PubMed2001

Working memory in schizophrenia: transient "online" storage versus executive functioning.

Working memory has been described as the temporary "online" storage and the subsequent manipulation and retrieval of information. It has been suggested that the prefrontal cortex is a primary site of working memory. Schizophrenia patients, who are thought to have prefrontal cortical dysfunction, have demonstrated inconsistent deficits on a variety of verbal and spatial working memory tests. This has led to questions about how to define and measure working memory, whether these deficits are distinct to one cognitive domain, and what role factors such as intelligence and symptoms play in working memory performance. We compared schizophrenia patients to normal comparison subjects in four separate studies. Based upon the results we recommend that working memory tests be characterized as either transient "online" storage and retrieval tasks (where short-term storage and retrieval of information is required) or executive-functioning working memory tasks (where storage, manipulation, and retrieval of information is required). The importance of clearly identifying which distinct aspects of working memory are assessed is discussed.

Adolescent↗

PubMed2000

Schizophrenia patients demonstrate a dissociation on declarative and non-declarative memory tests.

Declarative memory refers to the recall and recognition of factual information. In contrast, non-declarative memory entails a facilitation of memory based on prior exposure and is typically assessed with priming and perceptual-motor sequencing tasks. In this study, schizophrenia patients were compared to normal comparison subjects on two computerized memory tasks: the Word-stem Priming Test (n=30) and the Pattern Sequence Learning Test (n=20). Word-stem Priming includes recall, recognition (declarative) and priming (non-declarative) components of memory. The schizophrenia patients demonstrated an impaired performance on recall of words with relative improvement during the recognition portion of the test. Furthermore, they performed normally on the priming portion of the test. Thus, on tests of declarative memory, the patients had retrieval deficits with intact performance on the non-declarative memory component. The Pattern Sequence Learning Test utilizes a serial reaction time paradigm to assess non-declarative memory. The schizophrenia patients' serial reaction time was significantly slower than that of comparison subjects. However, the patients' rate of acquisition was not different from the normal comparison group. The data suggest that patients with schizophrenia process more slowly than normal, but have an intact non-declarative memory. The schizophrenia patients' dissociation on declarative vs. non-declarative memory tests is discussed in terms of possible underlying structural impairment.

Adult↗

PubMed2000

Chronically mentally ill patients with and without substance use disorders: a pilot study.

The study was designed to assess characteristics of chronic mentally ill patients with and without a substance use disorder. Study patients (n=48) had either psychiatric illness alone (they received conventional psychiatric rehabilitation) or dual diagnoses (they received mental illness and substance abuse services). All patients were administered the Brief Symptom Inventory (BSI), the Client Satisfaction Questionnaire, the Perceived Social Support Scales, and the Composite International Diagnostic Interview. Higher proportions of dually diagnosed patients had schizophrenia, had higher scores on the BSI, and were less satisfied with treatment.

Adult↗

PubMed2000

Mental health versus substance abuse treatment programs for dually diagnosed patients.

The aim of this study was to assess the similarities and differences of patients with co-existing psychiatric and substance use disorders attending treatment in either a mental health setting or a substance abuse treatment setting. A total of 129 patients were assessed, including 65 individuals from the substance abuse treatment center and 64 individuals from the mental health program. Treatment records were reviewed for diagnoses and sociodemographic data. While the two groups were highly similar with regard to age and ethnicity, there were significant differences in psychiatric profile, with the substance abuse treatment group having less severe diagnoses and no patients with schizophrenia, while the mental health treatment group had a majority of patients with schizophrenia. Other differences in the two groups, such as marital and parental status, disability status, and medical problems appeared to be directly linked with the aforementioned diagnostic profile. These data suggest important differences in characteristics of patients with comorbid disorders that appear to be dependent on the type of treatment program they attend. For the most effective management, integrated treatment programs should be aware of these differences and tailor service provision accordingly.

Adult↗

PubMed2000

A description of precipitants of drug use among dually diagnosed patients with chronic mental illness.

In this report, we describe patients' perceptions of the chronological occurrence of their mental illness and substance abuse. The patients were enrolled in a community mental health center and received dual diagnosis treatment from an affiliated psychiatric rehabilitation program. Using a questionnaire designed to address this issue, we assessed patients' perceptions of support currently being received at the treatment program and how beneficial they perceived this support to be. In addition, we assessed why substance use was a coping strategy in times of perceived stress early in life and whether this behavior has changed to date. Assessing the perception of the sequence of co-occurring disorders among patients enables us to better understand the factors that precipitate substance use and exacerbate mental illness. This knowledge may aid in the design of effective treatment strategies for this population of patients.

Adaptation, Psychological↗

PubMed2000

Severely mentally ill patients with and without substance use disorders: characteristics associated with treatment attrition.

We aimed to describe characteristics associated with attrition for patients in community mental health treatment with chronic mental illness with and without substance use disorders. Baseline assessments included symptom severity, treatment satisfaction, social support, and a structured diagnostic interview. Treatment attrition was assessed at six months. At six months, 36% of the dual diagnosis group (n = 25), and 61% of the mental illness alone group (n = 23) were lost to follow-up. Attrition in the dually diagnosed group tended to be associated with less satisfaction with treatment, and higher mean symptom scores. There were no characteristics associated with attrition in the group of patients with mental illness alone. However, client satisfaction tended to increase among the mental illness alone patients that were successfully followed. The dually diagnosed group that remained in treatment had a significantly lower mean treatment satisfaction score than the mental illness alone group at six months. This type of investigation should aid in patient care and evaluation of treatment programs for persons with severe mental illness and co-occurring substance use disorders.

Adult↗

PubMed2000

Combined oral oestradiol valerate-norethisterone treatment over three years in postmenopausal women: correlation between oestrogen levels and bone mineral density sites.

OBJECTIVE: To compare trabecular and compact bone response and relationship to oestrogen status using continuous oestradiol valerate 2 mg and norethisterone 0.7 mg daily as hormone replacement and to determine the therapeutic range of 17 beta-oestradiol. DESIGN: Open label trial. SETTING: Independent endocrine clinic SAMPLE: One hundred and thirty-one patients were compared at point of entry and at 36 months. METHODS: Postmenopausal women were assessed using a Lunar dual photon and single photon bone scanner, and bone mineral density of the lumbar spine, right hip and left forearm were annually correlated with 17 beta-oestradiol and oestrone levels over three years. Total alkaline phosphatase was compared between improvers and decliners of bone mineral density. RESULTS: Significant improvement in bone mineral density (P < 0.0001) occurred at all sites except the left forearm, where bone loss was prevented. There was no correlation between oestrogen levels and bone mineral density improvements at hip sites. However, in the lumbar spine larger improvements in bone mineral density occurred in women with 17 beta-oestradiol levels > 185 pmol/L compared with those below, which were statistically significant for those with 17 beta-oestradiol levels > 248 pmol/L. Bone turnover, as quanitifed by total alkaline phosphatase measurements, was suppressed in most patients, but there were no differences in the mean alkaline phosphatase levels between the best improvers and worst decliners for lumbar spine bone mineral density. Improvers had an age mean of 5.21 years greater than decliners (P = 0.01) and a mean duration difference since the menopause of 5 1 years compared with decliners (P = 0.007). CONCLUSION: This combined continuous preparation of hormone replacement therapy improves not only trabecular bone but prevents compact bone loss, and the data suggest that the therapeutic range of 17 beta-oestradiol is between 200 pmol/L and 350 pmol/L.

Administration, Oral↗

PubMed2000

Safety and tolerability of a rapidly escalating dose-loading regimen for risperidone.

BACKGROUND: Risperidone is an "atypical" antipsychotic with strong binding affinity for dopamine-2 and serotonin-2 receptors. Risperidone is often used to treat hospitalized patients who have acute psychotic decompensation, and the therapeutic target dose commonly used is 2 to 6 mg/day. The most common clinical practice is to titrate the dose of risperidone to the target therapeutic dose over several days. This study investigated the safety and tolerability of a rapid oral-loading regimen for risperidone developed to achieve therapeutic doses of this antipsychotic within 24 hours. METHOD: Rapid-loaded risperidone was initiated with 1 mg. Subsequent doses were increased by 1 mg every 6 to 8 hours up to 3 mg. Dose increases were contingent on tolerance of last administered dose. RESULTS: Of a sample of 11 consecutive inpatients admitted to an acute psychiatric facility who were treated with this protocol, 7 tolerated the most rapid titration, achieving a standing dose of 3 mg b.i.d. in 16 hours. Three required a slightly slower titration and achieved this target dose in 24 hours. One patient could not tolerate the 3-mg dose but tolerated a standing regimen of 2 mg t.i.d. No patient experienced serious extrapyramidal side effects, sedation, or any other adverse event during the rapid titration, and in no case did risperidone have to be discontinued. CONCLUSION: These results suggest that aggressive dosing of risperidone is well tolerated in most psychiatric inpatients.

Administration, Oral↗

PubMed1999

The nonlinear, complex sequential organization of behavior in schizophrenic patients: neurocognitive strategies and clinical correlations.

BACKGROUND: Thought disorder is a hallmark of schizophrenia and can be inferred from disorganized behavior. Measures of the sequential organization of behavior are important because they reflect the cognitive processes of the selection and sequencing of behavioral elements, which generate observable and analyzable behavioral patterns. In this context, sequences of choices generated by schizophrenic patients in a two-choice guessing task fluctuate significantly, which reflects an "oscillating dysregulation" between highly predictable and highly unpredictable subsequences within a single test session. In this study, we aimed to clarify the significance of dysregulation by seeing whether demographic, clinical, neuropsychological, and psychological measures predict the degree of dysregulation observed on this two-choice task. METHODS: Thirty schizophrenic patients repeatedly performed a LEFT or RIGHT key press that was followed by a stimulus, which occurred randomly on the left or right side of the computer screen. Thus, the stimulus location had nothing to do with the key press behavior. The range of key press sequence predictabilities as measured by the dynamical entropy was used to quantify the dysregulation of response sequences and reflects the range of fixity and randomness of the responses. A factor analysis was performed and step-wise multiple regression analyses were used to relate the factor scores to demographic, clinical, symptomatic, Wisconsin Card Sorting Test (WCST), and Rorschach variables. RESULTS: The LEFT/RIGHT key press sequences were determined by three factors: 1) the degree of win-stay/lose-shift strategy; 2) the degree of contextual influence on the current choice; and 3) the degree of dysregulation on the choice task. Demographic and clinical variables did not predict any of the three response patterns on the choice task. In contrast, the WCST and Rorschach test predicted performance on various factors of choice task response patterns. CONCLUSIONS: Schizophrenic patients employ several rules, i.e., "win-stay/lose-shift" and "decide according to the previous choice," that fluctuate significantly when generating sequences on this task, confirming that a basic behavioral dysregulation occurs in a single schizophrenic subject across a single test session. The organization or the "temporal architecture" of the behavioral sequences is not related to symptoms per se, but is related to deficits in executive functioning, problem solving, and perceptual organizational abilities.

Adult↗

PubMed1999

Cognitive functions in schizotypal personality disorder.

OBJECTIVE: Schizophrenia spectrum subjects have cognitive deficits in a variety of domains. Schizotypal personality disordered (SPD) subjects do not have many of the confounds seen in schizophrenic patients, but may have the same pattern of cognitive deficits in attention and executive functioning. HYPOTHESIS: We hypothesized that SPD subjects would have impairments on measures of attention, abstract reasoning, cognitive inhibition, working memory and verbal recognition memory when compared to normal subjects, and that these deficits would be intermediate to those observed in schizophrenic patients. METHOD: SPD subjects (N=20) were compared to age-, gender- and education-matched schizophrenic patients (N=20) and normal comparison subjects (N=20) on a battery of cognitive measures. RESULTS: The data were analyzed using standard statistical methods, including effect sizes. Using a conservative alpha level of 0.01, schizophrenic patients had deficits on many of these measures compared to normal subjects. Although the SPD subjects did not significantly differ from normal comparison subjects at the p < 0.01 level, there were trends (p < 0.019-0.028) toward impairment on measures of working memory and general intellectual functioning. On further effect size analyses, SPD subjects performed intermediate to normals and schizophrenic patients on measures of attention, abstract reasoning, cognitive inhibition, verbal working memory, recognition memory, and general intellectual functioning, with moderate to large effect sizes separating groups. CONCLUSIONS: These results suggest that SPD subjects have possible widespread cognitive deficits that are of lesser magnitude than those observed in schizophrenic patients.

Cognition↗

PubMed1999

Sensorimotor gating and thought disturbance measured in close temporal proximity in schizophrenic patients.

BACKGROUND: Sensorimotor gating abnormalities have been previously correlated with thought disturbance in schizophrenic patients. These correlative studies have led to the hypothesis that sensorimotor gating abnormalities may underlie thought disturbance. Several authors have cautioned, however, that this and similar hypotheses are supported by data recorded at different times or during resting states" and therefore incorrectly assume that the observed association represents a concurrent relationship. To address this issue, sensorimotor gating and thought disturbance were measured in close temporal proximity, thus strengthening the evidence for the association of these 2 abnormalities in schizophrenic patients. METHODS: Twenty-one schizophrenic men were assessed on measures of sensorimotor gating and thought disturbance. Sensorimotor gating was examined operationally via the use of prepulse inhibition. Thought disturbance was assessed via the Rorschach test measures of perceptual inaccuracy, disordered cognition, and the expression of normally repressed contents. Symptom rating scales (the Scale for the Assessment of Positive Symptoms and the alogia subscale of the Scale for the Assessment of Negative Symptoms) were also used. RESULTS: Deficient prepulse inhibition correlated significantly with 2 of the 3 Rorschach-derived thought disturbance measures. Prepulse inhibition was not correlated significantly with symptom rating scales. The Rorschach measure of impaired perceptual accuracy independently accounted for 60% of the variance in prepulse inhibition measures and contributed 35% of the unique variance beyond the effect attributable to the Scale for the Assessment of Positive Symptoms. CONCLUSIONS: Assessment of information processing and thought disturbance measures in close temporal proximity resulted in strong evidence that gating deficits correlate highly with measures of perceptual and reasoning disturbances. This relationship may form an important basis for the cognitive dysfunction observed among schizophrenic patients.

Acoustic Stimulation↗

PubMed1999

Sex differences in sensorimotor gating of the human startle reflex: all smoke?

RATIONALE: A recent report described sex differences in the effects of nicotine use and withdrawal on prepulse inhibition of acoustic startle (PPI), but no sex differences in PPI in non-smokers. OBJECTIVE: To determine whether previously reported male>female acoustic PPI reflect sex differences in smoking effects on PPI, rather than simple sex differences in the regulation of PPI. A retrospective analyses of >600 carefully screened normals tested over the past 12 years was completed. RESULTS: Male>female acoustic PPI was detected in analyses that included: 1) all subjects; or 2) self-declared non-smokers. CONCLUSIONS: Sex differences in PPI cannot be accounted for by smoking history, because they are present across a large sample of non-smoking normal controls.

Acoustic Stimulation↗

PubMed1998

The relationship between skin conductance hyporesponsivity and perseverations in schizophrenia patients.

BACKGROUND: It has been reported that approximately 45% of schizophrenia patients versus 10% of normal comparison subjects are classified as skin conductance hyporesponders (SCOR-HR: the lack of a robust orienting response) when exposed to innocuous tones. We studied the skin conductance orienting response (SCOR) of schizophrenia patients during the exposure to complex and abstract stimuli. We investigated two questions: 1) would the same percentage of schizophrenia patients be classified as SCOR-HR when the orienting stimuli are complex and abstract as when they are innocuous tones; and 2) whether SCOR-HR schizophrenia patients have associated frontally mediated neurocognitive deficits. METHODS: Thirty-one schizophrenia patients and 29 normal comparison subjects were presented with the Rorschach inkblot test while their SCORs were recorded. Schizophrenics were divided in two groups: SCOR-HR and SCOR responders. Demographic and clinical comparisons were made between the two groups. Rorschach responses were scored for the presence of perseverations. RESULTS: Forty-five percent of the schizophrenia patients were classified as SCOR-HR versus 10% of the normal comparison subjects. Among the schizophrenia patients, SCOR-HR was associated with increased perseverations, which were in turn correlated with the Scale for the Assessment of Negative Symptoms scores. CONCLUSIONS: It appears that SCOR-HR in schizophrenia is not a function of the "meaningfulness" of the stimuli. When SCOR status was combined with the measure of stuck-in-set perseverations, a pattern of results emerged lending indirect support to the hypothesis that relates SCOR-HR to frontal impairment and to the idea that SCOR-HR schizophrenia patients may represent a specific subgroup.

Adult↗