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Biomedical subjects

J Mintz

Publications and source records attributed to J Mintz.

At least 91 records · Page 5Linked to original sources

Rapid resolution of first episodes of mania: sleep related?

BACKGROUND: While sleep deprivation has been observed to precipitate mania, the relationship between sleep and resolution of mania is less well understood. We observed a rapid reversal of manic symptoms in several patients hospitalized for mania who slept many hours on Night 1 of hospitalization. We therefore undertook to study this relationship more systematically. METHOD: Charts for all patients admitted with a diagnosis of bipolar disorder, manic within a 2-year period were retrospectively reviewed. Patients were assigned to a group called "rapid responders" if improvement in symptoms, as described in progress notes, was moderate by Day 2 of hospitalization. Patients were "nonrapid responders" if improvement in symptoms was minimal or mild by Day 2. Sleep records, medications, and demographic data were obtained by researchers blind to the patients' response status on Day 2 of hospitalization. RESULTS: Compared with the 27 patients who did not have a rapid response, the 7 rapid responders were significantly more likely to (1) be in a first manic episode, (2) have a stressor associated with the onset of mania, (3) sleep more hours the first night of hospitalization, and (4) spend fewer days in the hospital. CONCLUSION: The possibility is raised that sleep restoration might induce a rapid antimanic response in patients experiencing their first episode of mania. The clinical implications of a rapid reversal of mania--including a reduction in number of hospital days--are discussed.

Adult↗

In vivo MR evaluation of age-related increases in brain iron.

PURPOSE: To assess the validity of an MR method of evaluating tissue iron. METHODS: The difference between the transverse relaxation rate (R2) measured with a high-field MR instrument and the R2 measured with a lower field instrument defines a measure termed the field-dependent R2 increase (FDRI). Previous in vivo and in vitro studies indicated that FDRI is a specific measure of tissue iron stores (ferritin). T2 relaxation times were obtained using two clinical MR instruments operating at 0.5 T and 1.5 T. T2 relaxation times were measured in the frontal white matter, caudate nucleus, putamen, and globus pallidus of 20 healthy adult male volunteers with an age range of 20 to 81 years. R2 was calculated as the reciprocal of T2 relaxation time. These in vivo MR results were correlated with previously published postmortem data on age-related increases of nonheme iron levels. RESULTS: The FDRI was very highly correlated with published brain iron levels for the four regions examined. In the age range examined, robust and highly significant age-related increases in FDRI were observed in the caudate and putamen. The correlations of age and FDRI in the globus pallidus and white matter were significantly lower and did not have statistical significance. CONCLUSIONS: The data provide additional evidence that FDRI is a specific measure of tissue iron stores. The data also show that age-related increases in tissue iron stores can be quantified in vivo despite significant age-related processes that oppose the increase in R2 caused by iron. These results are relevant to the investigation of neurodegenerative processes in which iron may catalyze toxic free-radical reactions.

Adult↗

Field dependent transverse relaxation rate increase may be a specific measure of tissue iron stores.

The degree to which MRI magnet field strength affects measured transverse relaxation rates (R2) defines a measure termed the field dependent R2 increase (FDRI). We report here the results of in vivo and in vitro experiments that were conducted to evaluate whether FDRI is a potentially useful measure of tissue iron stores. T2 relaxation times were obtained using two clinical MRI instruments operating at 0.5 and 1.5 Tesla, and relaxation rates (R2) were calculated as the reciprocal of T2. The in vivo experiment measured R2 in human brain frontal white matter, caudate nucleus, putamen, and globus pallidus. The FDRI was very highly correlated with published brain iron levels for the four regions examined. The in vitro experiment measured R2 in agarose gel-based phantoms containing physiologic forms and amounts proteins involved in iron storage and transport (ferritin, apoferritin, transferrin, and apotransferrin). Significant field dependence was observed only for the ferritin phantoms. The differences in the R2 values obtained at the two field strengths were striking, and were proportional to the ferritin levels of the phantoms. These studies suggest that FDRI may be a specific measure of tissue ferritin. The quantitative significance of the results to imaging and possible applications to the clinical investigation of pathologic states are discussed.

Adult↗

Reliability of in vivo volume measures of hippocampus and other brain structures using MRI.

Volume reductions of the hippocampus are associated with Alzheimer's disease, schizophrenia, and epilepsy. We used clinically available MRI methods (2D acquisition; inversion recovery and calculated T2 images; 3 mm contiguous slices) that optimize image contrast, quality, and resolution and standardized positioning protocols to maximize the in vivo accuracy (test-retest reliability) of brain volume measurements in volunteers who were scanned two or three times. Volunteers were scanned in the same MRI instrument (intrascanner reliability) as well as in two different instruments (interscanner reliability). A single rater obtained brain volume measures of seven contiguous slices centered on the anterior commissure. The in vivo intrascanner reliability for measures of anterior hippocampus and ventricular volumes was very good, with reliability coefficients [intraclass r (rxx)] ranging between .855 and .997, and a median coefficient of variation (CV) of 6.4%. Reliability was good for amygdala (rxx of .740 and .764) and for total frontal and temporal lobe volumes and white matter volume measures (rxx ranging between .640 and .823, median coefficient of variation was 3.2%). Overall, interscanner reliability was also good. We discuss the implications of our results relative to the possible clinical utility of hippocampal quantification and the feasibility of prospective studies aimed at quantifying progressive neurodegeneration.

Adult↗

Prediction of response to haloperidol dose reduction by Span of Apprehension measures for treatment-refractory schizophrenic patients.

Thirteen treatment-refractory schizophrenic patients participated in a haloperidol reduction study. Two of the subjects were unable to tolerate medication reduction. These subjects were comparable to the other patients in terms of initial clinical variables but were outliers on baseline accuracy and reaction time measures from the Span of Apprehension. The results suggest that aspects of basic visual processing and motor response speed may identify patients who require higher neuroleptic doses.

Adult↗

Patients' perceptions of family emotional climate and outcome in schizophrenia.

Thirty-nine chronic schizophrenic male out-patients and their relatives were interviewed separately to assess their perceptions of their current relationships. Two simple 5-point rating scales predicted the risk of psychotic exacerbation during a one-year follow-up: patients' perceptions of the relatives' attitudes towards them, and patients' own attitudes towards the relatives. Survival analysis of data in a 2 x 2 factorial--combining degree of contact with the key relatives and the patients' perceptions of their relatives--found that patients in frequent contact with a positively perceived relative had significantly better survival rates without psychotic exacerbation. Patients' perceptions of their relatives may help identify patients at risk of exacerbation of their illness.

Adolescent↗

Systematic dosage reduction in treatment-resistant schizophrenic patients.

Thirteen treatment-resistant, chronically institutionalized schizophrenic patients on high-dose neuroleptic (the equivalent of at least 50 mg of haloperidol (HPL) daily) were transferred to a special research ward for a trial of systematic dosage reduction. In these 13 patients, it was possible to reduce the dose of HPL from 63.1 mg/day (SD +/- 12.5, range = 50-80 mg/day) to 23.1 mg/day (SD +/- 16.3, range = 0-65 mg/day) over a mean period of 32 weeks (SD +/- 9.6, range = 15-46 weeks). Their total Brief Psychiatric Rating Scale (BPRS) scores were improved (p = .04), they definitely experienced fewer extrapyramidal side effects (p = .01), and 6 of the patients showed global improvement. On several behavioral rating scales there was, if anything, an improvement in negativistic behavior. The substantial dosage reduction was paralleled by a comparable drop in plasma levels. HPL plasma levels at baseline were 38.8 ng/mL (SD +/- 17.8, range = 21.5-69.5 ng/mL) and at the lowest effective dose were 12.4 ng/mL (SD +/- 10.3, range = 0-43.4 ng/mL).

Adult↗

Treatments of depression and the functional capacity to work.

This study evaluated the effects of antidepressants and psychotherapy on work impairment in depressed patients. Original databases from 10 published treatment studies were compiled and analyzed (N = 827). Functional work impairment was common at baseline, manifested by unemployment (11%) or on-the-job performance problems (absenteeism, decreased productivity, interpersonal problems, 44%). Generally, work outcomes were good when treatment was symptomatically effective, but the trajectories of work restoration and symptom remission were different, with work recovery appearing to take considerably longer. Relapse was an important determinant of long-term occupational outcome, particularly for seriously ill patients for whom relapse meant rehospitalization or other profound social disruption. Affective impairment was distinguished from functional impairment, with the former characterizing milder depression and the latter characterizing moderate to severe depression. Some methodological recommendations are discussed.

Absenteeism↗

Prodromal symptoms and signs of bipolar relapse: a report based on prospectively collected data.

Prospectively collected data on 19 recently hospitalized patients with bipolar disorder were examined for prodromal changes preceding relapse. The 4-month periods before six manic and six depressive relapses were compared with each other and with a comparable period for seven patients who did not relapse. The Brief Psychiatric Rating Scale was used to assess symptoms. Significant elevations in unusual thought content were found 1 month before manic relapse. Depressive relapsers evidenced higher levels of conceptual disorganization throughout the prerelapse period. Nonrelapsers showed very stable symptom profiles.

Adult↗

Concurrent and predictive electrodermal correlates of symptomatology in recent-onset schizophrenic patients.

Electrodermal activity and symptomatology were interrelated in a group of 56 male and 13 female recent-onset schizophrenic patients. Electrodermal activity was indexed by the frequency of nonspecific skin conductances responses and the number of trials to habituation of the skin conductance orienting response. Symptomatology was assessed by the Brief Psychiatric Rating Scale (BPRS) on two separate test occasions. The first test occasion was during the inpatient period when psychotic symptoms were prevalent and medications were variable. The second test occasion was several months later during an outpatient period when symptoms were stabilized and medications held constant. Electrodermal activity was positively and significantly related to a number of symptoms in male patients, most reliably the BPRS factors Activation and Hostility/Suspiciousness. These relationships were most consistent during the outpatient period. Of particular theoretical interest, greater electrodermal activity during the inpatient period was associated with greater outpatient psychopathology. The results suggest that heightened inpatient electrodermal activity is predictive of poor short-term symptomatic recovery in recent-onset, acute, male schizophrenic patients.

Adolescent↗

Developmental Processes in Schizophrenic Disorders: longitudinal studies of vulnerability and stress.

The Developmental Processes in Schizophrenic Disorders project is a longitudinal study of schizophrenic patients who have recently had a first episode of psychosis. The project focuses on discriminating characteristics of schizophrenic patients that are "stable vulnerability indicators," "mediating vulnerability factors," and "episode indicators" by comparing normal subjects to schizophrenic patients assessed in clinically remitted and psychotic states. A parallel project goal is to identify predictors of relapse, social and work impairment, and illness course among potential psychobiological vulnerability factors and environmental potentiating factors. Hypothesized vulnerability factors and potential environmental stressors are examined first under standardized maintenance antipsychotic medication conditions for at least 1 year. Patients showing stable remission of psychosis after 1 year of maintenance antipsychotic medication are invited to enter drug crossover and withdrawal protocols to determine the need for continuous antipsychotic medication. Vulnerability and stress factors are again assessed. A summary of results to date is presented. Deficits in early components of processing visual arrays and in sustained discrimination of successive ambiguous perceptual inputs are relatively stable across psychotic and clinically remitted states in the schizophrenic patients. Performance on a vigilance task demanding active, working memory also remains abnormal during clinical remission but covaries significantly with psychotic state and is a candidate for a mediating vulnerability factor. Autonomic activation level does not appear to be an enduring vulnerability factor, but it predicts the extent of short-term symptomatic recovery and may mediate the impact of stressors. Under conditions of standardized, injectable antipsychotic medication, independent stressful life events and highly critical attitudes toward the patient in the social environment predict relapse risk. Prospective data suggest that signs and symptoms prodromal to psychotic relapse may be present in about 60 percent of patients.

Adolescent↗

Technique for training schizophrenic patients in illness self-management: a controlled trial.

OBJECTIVE: To determine whether schizophrenic outpatients receiving low-dose neuroleptic therapy could learn and retain complex information and skills related to self-management of their illness, a novel technique of teaching, using cognitive and behavioral methods, was designed to compensate for the patients' learning disabilities. METHOD: The subjects were 41 patients with DSM-III-R schizophrenia who were receiving constant maintenance neuroleptic drug therapy. They were randomly assigned to structured, modularized skills training or to supportive group psychotherapy. RESULTS: The patients who received skills training made significant gains in each of the areas taught, while those participating in group therapy did not. The skills learned during training were retained without significant erosion over a 1-year follow-up period. CONCLUSIONS: The effectiveness of modularized teaching of illness self-management skills to schizophrenic patients appears to be largely independent of baseline psychology and symptom improvement. Such an approach is useful for overcoming or compensating for the enduring cognitive and information processing deficits commonly found in schizophrenia.

Activities of Daily Living↗

Haloperidol plasma levels and clinical response: a therapeutic window relationship.

OBJECTIVE: The purpose of the study was to assess the relationship between plasma haloperidol and clinical response. METHOD: Sixty-nine newly admitted drug-free schizophrenic men were randomly assigned to receive haloperidol, 5, 10, or 20 mg daily for 4 weeks, and clinical response was measured at the end of the fixed-dose period. Haloperidol was assayed by a sensitive and specific radioimmunoassay. RESULTS: The authors found a curvilinear relationship between clinical response and plasma haloperidol during fixed-dose treatment, with an apparent optimum between 5 and 12 ng/ml. When plasma levels above 12 ng/ml were lowered to the 5-12 ng/ml range, all patients improved to varying degrees and no patient deteriorated. When plasma levels of nonresponders within this therapeutic window were raised above 12 ng/ml (as in routine practice), they, on balance, deteriorated in that they became more dysphoric. With the 20-mg dose, half the patients had plasma levels above 12 ng/ml. CONCLUSIONS: In this sample of newly admitted schizophrenic men, optimal clinical response occurred with a plasma haloperidol range of 5-12 ng/ml.

Adult↗

Acquisition and retention of skills training methods in chronic schizophrenic outpatients.

Forty-one DSM-III-R schizophrenic subjects on constant, low-dose maintenance neuroleptic drug therapy (5-10 mg of fluphenazine decanoate intramuscularly every 2 weeks) were randomly assigned to structured and modularized skills training or to supportive group psychotherapy. The skills training was designed by using cognitive and behavioral methods to compensate for the learning disabilities that plague many schizophrenic patients. Skill acquisition was assessed by using quantified performance on standardized role-play tests. Subjects who received skills training made significant gains in each of the areas taught, whereas those who participated in the control psychotherapy group did not. The knowledge and skills learned during training were retained without significant erosion over a 1-year followup period. These results suggest that the use of structured principles of learning and cognitive therapy can effectively train schizophrenics in skill areas pertinent to the self-management of their illness.

Adult↗

Combined use of alcohol and nicotine gum.

This study evaluated the effects of chewing nicotine gum immediately before and just after drinking a moderate amount of alcohol. Four research questions were addressed. First, does chewing nicotine gum prior to drinking alcohol attenuate the increased craving to smoke that is typically associated with alcohol use? Second, does drinking prior to chewing reduce the gum's effectiveness? Third, are significant side effects observed with nicotine gum, and is their severity affected by alcohol use? Finally, can we identify subjects who are more likely to respond well to the gum on the basis of smoking history or pattern or other descriptive-demographic, psychologic, or historical variables? Smokers who had abstained for at least 12 h were studied in a fully crossrandomized experimental design that contrasted nicotine gum (before or after drinking) versus sugarless gum, and alcohol versus a no-alcohol comparison condition. Nicotine gum use was associated with significantly greater immediate reduction in craving to smoke, regardless of whether it preceded or followed alcohol, but the effects were weak and short-lived in either case. Moderate use of alcohol after chewing the gum eliminated virtually all of its beneficial effects. Mild side effects were common with nicotine gum, but equally so regardless of alcohol use. A small battery of demographic and historical variables failed to identify those subjects who responded well to nicotine gum.

Adult↗

T2 hyperintense foci on magnetic resonance images of schizophrenic patients and controls.

High resolution magnetic resonance imaging (MRI) of the brain was performed on 18 male schizophrenic patients and 15 male normal control subjects using an identical imaging protocol. The number and size of T2 hyperintense foci were clinically quantified by an academic radiologist. Large foci (greater than or equal to 3 mm in diameter) were observed more frequently on patient images (7/18) than on control images (1/15). The imaging protocol detected high rates of focal hyperintensities, but no differences between patients and controls were noted in the total affected brain area (sum of focal areas) or in the presence or absence of foci.

Adult↗

Implications of therapist effects for the design and analysis of comparative studies of psychotherapies.

Technical reasons are presented as to why therapist should be included as a random design factor in the nested analysis of (co)variance (AN[C]OVA) design commonly used in psychotherapy research. Incorrect specification of the ANOVA design can, under some circumstances, result in incorrect estimation of the error term, overly liberal F ratios, and an unacceptably high risk of Type I errors. Review of studies indicates that the great majority of investigators continue to ignore this issue. Computer simulation studies revealed that considerable bias can be introduced by not specifying therapist as a random term. Finally, a reanalysis is presented of data from 10 psychotherapy outcome studies that indicated that therapist effects vary considerably and at times can be large. More recent studies that implement better quality controls appear to demonstrate less variance due to therapist. The implications of these results for the design of future studies are discussed.

Analysis of Variance↗