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Biomedical subjects

Judith Jaeger

Publications and source records attributed to Judith Jaeger.

16 recordsLinked to original sources

Development and reliability of the HAM-D/MADRS interview: an integrated depression symptom rating scale.

The Hamilton Rating Scale for Depression (HAM-D) and the Montgomery-Asberg Depression Rating Scale (MADRS), two widely used depression scales, each have unique advantages and limitations for research. The HAM-D's limited sensitivity and multidimensionality have been criticized, despite the scale's popularity. The MADRS, designed to be sensitive to treatment changes, is briefer and more uniform. A limitation of the MADRS is the lack of a structured interview, which may affect reliability. The HAM-D and the MADRS are often used conjointly as endpoints in depression trials. We designed a hybrid questionnaire that allows administration of MADRS and 31 HAM-D items simultaneously. Seventy mood disorder patients (60 bipolar I, 10 major depressive disorder) were administered the HAM-D/MADRS Interview (HMI) as part of a larger study. Interrater reliability for 50 patients was excellent for the HAM-D and the MADRS (ICC=0.97-0.98). MADRS item reliabilities (ICC=0.86-0.97) were higher than obtained in studies that did not use a structured interview. Reliability coefficients for seven HAM-D(31) 'atypical' symptoms ranged from 0.77 to 0.95. HMI was highly correlated with the Global Clinical Impressions Scale. This is the first study we know of to investigate the reliability of a structured interview of either the MADRS or of the HAM-D(31). The HMI provides an easily administered, reliable method of rating depression severity which may improve consistency and validity of study findings.

Adolescent↗

Neurocognitive deficits and disability in major depressive disorder.

Disability in life functioning is an important and poorly understood consequence of major depressive disorder (MDD). Mood symptoms do not account for the magnitude of disability resulting from MDD. Impairments in several domains of neurocognitive (NC) functioning have been shown to interfere with functionality in other psychiatric populations. These deficits, also present in MDD, may play a significant role in disability experienced by many with this disorder. The aim of this study was to examine the degree to which NC deficits, independent of affective and psychotic symptoms, explain functional outcome 6 months following hospitalization for a major depressive episode. Participants with an MDD diagnosis (N=48) received NC testing and symptom ratings while in the hospital. These procedures were repeated, along with functionality ratings, 6 months later. Six-month NC performance was strongly associated with functionality ratings after covariation for residual depression. Selected NC domains tested at baseline were predictive of functionality at 6 months. These data indicate that NC deficits, at least for some MDD sufferers, play an important role in functional recovery. New treatments, whether pharmacologic or rehabilitative, may be required to help affected patients accommodate neurocognitively based performance deficits at work, at home and in the community.

Activities of Daily Living↗

Associating functional recovery with neurocognitive profiles identified using partially ordered classification models.

Neurocognitive deficits are a core feature of schizophrenia and a significant cause of functional disability. However, targeting these deficits with new treatment approaches will only yield functional improvements if those cognitive operations that are responsible for different dimensions of functional recovery can be identified. A major challenge is that conventional neuropsychological tests, the most practical tools for broadly sampling cognitive functions in treatment trials, are polyfactorial, so that task performance is influenced by multiple cognitive operations. Hence, it is difficult to pinpoint exactly for which cognitive operations a low scoring subject may have poor functionality. We have previously applied in a neuropsychological test battery administered to 220 patients having schizophrenia or schizoaffective disorder, Bayesian statistical methods (yielding partially ordered sets, or posets) designed to mimic the expert analysis of a neuropsychologist by classifying patients into discrete groupings or "states" each having a unique cognitive profile. Here, we report on the association of attributes describing these states (viz. working memory, capacity for divergent thinking, cognitive flexibility and psychomotor speed) with two domains of functional outcome (work/education and residential functioning) rated up to 18 months later. After multiplicity correction, only working memory was associated with work/education outcome. While working memory was not associated with residential outcome, the remaining three attributes were. These findings suggest that different neurocognitive operations may be responsible for different outcome domains. Findings support the use of the poset methodology for clarifying patterns of relationships between discrete neurocognitive attributes and domains of functional outcome.

Adolescent↗

Distinguishing neurocognitive functions in schizophrenia using partially ordered classification models.

Current methods for statistical analysis of neuropsychological test data in schizophrenia are inherently insufficient for revealing valid cognitive impairment profiles. While neuropsychological tests aim to selectively sample discrete cognitive domains, test performance often requires several cognitive operations or "attributes." Conventional statistical approaches assign each neuropsychological score of interest to a single attribute or "domain" (e.g., attention, executive, etc.), and scores are calculated for each. This can yield misleading information about underlying cognitive impairments. We report findings applying a new method for examining neuropsychological test data in schizophrenia, based on finite partially ordered sets (posets) as classification models. A total of 220 schizophrenia outpatients were administered the Positive and Negative Symptom Scale (PANSS) and a neuropsychological test battery. Selected tests were submitted to cognitive attribute analysis a priori by two neuropsychologists. Applying Bayesian classification methods (posets), each patient was classified with respect to proficiency on the underlying attributes, based upon his or her individual test performance pattern. Twelve cognitive "classes" are described in the sample. Resulting classification models provided detailed "diagnoses" into "attribute-based" profiles of cognitive strength/weakness, mimicking expert clinician judgment. Classification was efficient, requiring few measures to achieve accurate classification. Attributes were associated with PANSS factors in the expected manner (only the negative and cognition factors were associated with the attributes), and a double dissociation was observed in which divergent thinking was selectively associated with negative symptoms, possibly reflecting a manifestation of Kraepelin's hypothesis regarding the impact of volitional disturbances on thought. Using posets for extracting more precise cognitive information from neuropsychological data may reveal more valid cognitive endophenotypes, while dramatically reducing the amount of testing required.

Adult↗

Community-based vocational rehabilitation: effectiveness and cost impact of a proposed program model.

OBJECTIVE: To study the vocational, service use and relative cost impact for schizophrenia or schizoaffective disorder of an innovative community-based vocational rehabilitation program. METHOD: Participants were consecutive enrollees in a community-based vocational rehabilitation program who had remained in the program for at least 1 year. Lifetime vocational history and mental health service utilization for 2 years prior and up to 4 years subsequent to program enrollment were studied. Retrospective data were collected using a questionnaire completed by the patient and available family and case workers, patient interview and chart review. RESULTS: Months in paid work increased after enrollment, while earned income did not (most work was low wage and/or part-time). Annual inpatient days decreased precipitously, a change which could not be explained by hospitalization trends during the same period. Average relative cost units, based on charges for mental health services used, dropped over 70% following enrollment. CONCLUSIONS: Community-based vocational rehabilitation may be cost-effective in this population, largely as a result of its impact on hospitalizations and utilization of the most costly services. Such programs represent an important alternative to supported employment that may be particularly suited to cognitively or functionally impaired patients unwilling or unable to work in a competitive environment.

Adult↗

Premorbid adjustment in bipolar disorder: comparison with schizophrenia.

Knowledge that poor premorbid adjustment (PMA) precedes illness onset in many schizophrenia cases can facilitate early detection. Increasing consideration is being given to a similar early detection strategy for bipolar disorder (BPD). Results of this preliminary investigation comparing PMA in BPD (N = 53) and schizophrenia (N = 39) outpatients revealed a significant difference at the late adolescent (F[1,58] = 4.499, p = 0.038) stage only, with specific differences in two areas of PMA: adaptation to school (t [58] = 1.83, p = 0.036) and social sexual functioning (t [58] = 2.441, p = 0.009). However, mood state may affect some PMA ratings in BPD. Depression ratings were not correlated with reported late adolescent PMA, but a significant, positive correlation was found for the childhood stage (r = 0.32, p = 0.02). Findings fail to support a trend similar to schizophrenia of deteriorating PMA in BPD; however, the approach to investigations of PMA in BPD may need to be reconsidered.

Adaptation, Psychological↗

Psychosocial outcome in bipolar I patients with a personality disorder.

This study examined whether comorbid personality disorders and other clinical factors were predictive of functional morbidity in bipolar I disorder. Fifty-one participants with a diagnosis of bipolar I were assessed for personality disorders and administered measures of symptomatic and functional outcomes approximately 1 year after a psychiatric hospitalization. Forty-five percent of the sample met criteria for at least one personality disorder, and patients with a personality disorder reported higher levels of residual symptoms at the time of assessment. Two thirds of participants displayed compromised functional outcomes. The three outcome domains examined (i.e., occupational, residential, social/leisure) were related to a range of clinical characteristics, and for all three, either the presence of a personality disorder diagnosis or maladaptive trait scores was associated with impaired functioning. These relationships, however, were not independent of mood symptoms according to multivariate analysis. Residual depression predicted poorer residential and social/leisure outcomes independent of personality disorders or maladaptive traits.

Activities of Daily Living↗

Quantitative craniofacial anomalies in a racially mixed schizophrenia sample.

BACKGROUND: The observation that some patients with schizophrenia display subtly anomalous craniofacial features dates back to the early 1900s and has recently been hypothesized to reflect disrupted prenatal development also involving the brain. Most studies to date have used observer ratings rather than physical measurements and have studied only Caucasian samples. Our objective was to determine whether schizophrenia is associated with craniofacial anomalies applying quantitative methods in Caucasian and African American subjects. METHODS: Participants were 32 Caucasian and 20 African American outpatients aged 18 to 60, meeting Structured Clinical Interview for DSM-IV (SCID) confirmed criteria for schizophrenia/schizoaffective disorder, recently discharged from a psychiatric hospital in Queens, New York. The healthy control subjects were recruited through local advertisements and were individually matched to the patient sample on gender, race, and age. RESULTS: Thirty-two measurements of the head and face reflecting all regions of potential developmental significance were taken according to published methods and validated for this study. Significantly greater skull base width [F(1,51) = 13.11, p = .0005] and greater height of the cutaneous lower lip [F(1,51) = 7.90, p = .0059] were found among patients after applying multiplicity correction. Statistical correction for group differences in body weight did not alter the findings. CONCLUSIONS: Findings agree with the two major anthropometric studies in schizophrenia.

Adolescent↗

Four-year angiographic and intravascular ultrasound follow-up of patients treated with sirolimus-eluting stents.

BACKGROUND: Despite the proven superiority of sirolimus-eluting stents (SESs) compared with bare stents in the first year after implantation, long-term outcomes of patients treated with these novel devices remain unknown. Our goal was to evaluate the clinical, angiographic, and intravascular ultrasound (IVUS) outcomes of patients treated with SESs 4 years after implantation. METHODS AND RESULTS: The study included 30 patients treated with sirolimus-eluting Bx Velocity stenting (slow release [SR; n=15] and fast release [FR; n=15]). Twenty-six patients underwent 4-year angiographic and IVUS follow-up and had matched assessments at all time points (index and 4-, 12-, 24-, and 48-month follow-up). One death occurred during the study period in a patient with a patent SES. There were no target-vessel revascularizations or thromboses between 2- and 4-year follow-up examinations. There was no stent thrombosis, target-lesion revascularization, death, or myocardial infarction in the SR group up to 4 years. Cumulative event-free survival rate was 87% for the total population (80% in the FR group and 93% in the SR group). In-stent late loss was slightly greater in the FR group (0.41+/-0.49 mm) than the SR group (0.09+/-0.23) after 4 years. One patient in the FR group had a 52% in-stent restenosis lesion. Percent neointimal hyperplasia volume, as detected by IVUS, remained minimal after 4 years (FR=9.1% and SR=5.7%). CONCLUSIONS: This study confirms the longevity of the optimal outcomes observed in patients treated with sirolimus-eluting Bx Velocity stents 4 years after implantation. In-stent lumen dimensions remained essentially unchanged at 4-year follow-up, particularly in the population treated with the currently available SES (SR formulation).

Cardiovascular Diseases↗

Disrupted in schizophrenia 1 (DISC1): association with schizophrenia, schizoaffective disorder, and bipolar disorder.

Schizophrenia, schizoaffective disorder, and bipolar disorder are common psychiatric disorders with high heritabilities and variable phenotypes. The Disrupted in Schizophrenia 1 (DISC1) gene, on chromosome 1q42, was originally discovered and linked to schizophrenia in a Scottish kindred carrying a balanced translocation that disrupts DISC1 and DISC2. More recently, DISC1 was linked to schizophrenia, broadly defined, in the general Finnish population, through the undertransmission to affected women of a common haplotype from the region of intron 1/exon 2. We present data from a case-control study of a North American white population, confirming the underrepresentation of a common haplotype of the intron 1/exon 2 region in individuals with schizoaffective disorder. Multiple haplotypes contained within four haplotype blocks extending between exon 1 and exon 9 are associated with schizophrenia, schizoaffective disorder, and bipolar disorder. We also find overrepresentation of the exon 9 missense allele Phe607 in schizoaffective disorder. These data support the idea that these apparently distinct disorders have at least a partially convergent etiology and that variation at the DISC1 locus predisposes individuals to a variety of psychiatric disorders.

Adult↗

Basic neuropsychological dimensions in schizophrenia.

Neuropsychological (NP) studies in schizophrenia often require data reduction to avoid statistical type I error from multiple comparisons. Typically, this involves grouping measures into domains defined by experts a priori based on delineations validated in brain-injured but not schizophrenia samples (e.g. attention, executive functioning, memory, language visuospatial, motor). Component measures are arbitrarily selected and validity may not generalize to different samples or within the same sample over time. One solution to these problems is illustrated using neurocognitive subdomains based on recent schizophrenia literature, and validated with data from a longitudinal study (156 subjects) involving repeated NP testing (baseline--within 6 months of hospital discharge--and 6 and 18 months later). A priori subdomains were grouped and submitted to principal component analysis (PCA) at each time point. Longitudinal stability of the resulting factors was tested by computing congruency coefficients. Six stable factors were extracted having good construct, divergent and predictive validity. Five neuropsychological measures frequently studied in schizophrenia were not correlated with these factors, suggesting that they should be maintained as independent neurocognitive subdomains. Distinct factors for executive functioning, verbal memory and motor functions could not be validated; this raises concerns about conclusions of previous studies regarding the pattern, severity and correlates of specific neurocognitive functions in schizophrenia.

Adult↗

Two-year angiographic and intravascular ultrasound follow-up after implantation of sirolimus-eluting stents in human coronary arteries.

BACKGROUND: The safety and efficacy of sirolimus-eluting stenting have been demonstrated, but the outcome of patients treated with this novel technology beyond the first year remains unknown. We sought to evaluate the angiographic, intravascular ultrasound (IVUS), and clinical outcomes of patients treated with sirolimus-eluting stents 2 years after implantation. METHODS AND RESULTS: This study included 30 patients treated with sirolimus-eluting Bx Velocity stenting (slow release [SR], n=15, and fast release [FR], n=15) in São Paulo, Brazil. Twenty-eight patients underwent 2-year angiographic and IVUS follow-up. No deaths occurred during the study period. In-stent late loss was slightly greater in the FR group (0.28+/-0.4 mm) than in the SR group (-0.09+/-0.23 mm, P=0.007). No patient had in-stent restenosis. At 2-year follow-up, only 1 patient (FR group) had a 52% diameter stenosis within the lesion segment, which required repeat revascularization. The target-vessel revascularization rate for the entire cohort was 10% (3/30) at 2 years. All other patients had < or =35% diameter stenosis. Angiographic lumen loss at the stent edges was also minimal (in-lesion late loss was 0.33+/-0.42 mm [FR] and 0.13+/-0.29 mm [SR]). In-stent neointimal hyperplasia volume, as detected by IVUS, remained minimal after 2 years (FR= 9.90+/-9 mm3 and SR=10.35+/-9.3 mm3). CONCLUSIONS: This study demonstrates the safety and efficacy of sirolimus-eluting Bx Velocity stents 2 years after implantation in humans. In-stent lumen dimensions remained essentially unchanged at 2-year follow-up in the 2 groups, although angiographic lumen loss was slightly higher in the FR group. Restenosis "catch-up" was not found in our patient population.

Combined Modality Therapy↗

Sirolimus-eluting stent for the treatment of in-stent restenosis: a quantitative coronary angiography and three-dimensional intravascular ultrasound study.

BACKGROUND: We have previously reported the safety and effectiveness of sirolimus-eluting stents for the treatment of de novo coronary lesions. The present investigation explored the potential of this technology to treat in-stent restenosis. METHODS AND RESULTS: Twenty-five patients with in-stent restenosis were successfully treated with the implantation of 1 or 2 sirolimus-eluting Bx VELOCITY stents in São Paulo, Brazil. Nine patients received 2 stents (1.4 stents per lesion). Angiographic and volumetric intravascular ultrasound (IVUS) images were obtained after the procedure and at 4 and 12 months. All vessels were patent at the time of 12-month angiography. Angiographic late loss averaged 0.07+/-0.2 mm in-stent and -0.05+/-0.3 mm in-lesion at 4 months, and 0.36+/-0.46 mm in-stent and 0.16+/-0.42 mm in-lesion after 12 months. No patient had in-stent or stent margin restenosis at 4 months, and only one patient developed in-stent restenosis at 1-year follow-up. Intimal hyperplasia by 3-dimensional IVUS was 0.92+/-1.9 mm(3) at 4 months and 2.55+/-4.9 mm(3) after 1 year. Percent volume obstruction was 0.81+/-1.7% and 1.76+/-3.4% at the 4- and 12-month follow-up, respectively. There was no evidence of stent malapposition either acutely or in the follow-up IVUS images, and there were no deaths, stent thromboses, or repeat revascularizations. CONCLUSION: This study demonstrates the safety and the potential utility of sirolimus-eluting Bx VELOCITY stents for the treatment of in-stent restenosis.

Combined Modality Therapy↗

The multidimensional scale of independent functioning: a new instrument for measuring functional disability in psychiatric populations.

The Multidimensional Scale of Independent Functioning (MSIF) is a new instrument for rating functional disability in psychiatric outpatients. The MSIF differs from other disability rating scales by providing discrete ratings of (1) role responsibility, (2) presence and level of support, and (3) performance quality. The MSIF, which consists of a semistructured interview and detailed rating anchors, was validated in 114 psychiatric outpatients. The instrument had good criterion, discriminative, interrater, and construct validity. Correlations between comparable ratings on the Social Adjustment Scale II (SAS II) ranged from 0.78 to 0.86. Nevertheless, redundancy analysis using canonical correlation demonstrated that, although the two instruments overlap, the MSIF contains information that is not contained in the SAS II. Furthermore, there was only modest shared variance with conceptually non-overlapping subscales in the SAS II. Interrater reliability (intraclass correlation coefficients) ranged from 0.74 to 1.00 for global and subscale scores. MSIF subscales performed as expected with respect to external validators such as hours of employment, earned income, supported versus nonsupported employment and housing, and mainstream versus nonmainstream educational status. MSIF global ratings were modestly correlated with IQ and psychopathology ratings, consistent with reports in the literature. Construct validity, estimated using Cronbach's alpha coefficient, was 0.72. The MSIF is a promising new instrument designed to circumvent several limitations with existing functional outcome instruments for longitudinal studies, intervention research, and services research.

Demography↗

No evidence for phenotypic variation between probands in case-control versus family-based association studies of schizophrenia.

Traditional case-control genetic association studies utilizing unrelated probands are often used interchangeably with family-based designs to detect genes for complex psychiatric disorders. This strategy may be limited, however, if significant phenotypic variation exists between probands enrolled in these two types of studies. The present study compared 37 probands enrolled in a case-control study of schizophrenia with 37 age-, sex-, and ethnically matched probands enrolled in a family-based study of schizophrenia. Age of onset of illness was compared as well as performance on a battery of cognitive tests assessing attention, working memory, executive function, and verbal memory. Results revealed no significant differences in age of onset between the two groups or on any measure of cognitive performance. These data do not support reports of significant phenotypic variation between probands in case-control and family-based studies, and suggest that studies utilizing family-based approaches may be used to replicate reports of association made with case-control designs in schizophrenia.

Adult↗