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1.  Prediction of Real World Functional Disability in Chronic Mental Disorders: A Comparison of Schizophrenia and Bipolar Disorder 
The American journal of psychiatry  2010;167(9):1116-1124.
OBJECTIVE
Schizophrenia (SZ) and Bipolar Disorder (BD) are associated with multidimensional disability. This study examined differential predictors of functional deficits between the disorders.
METHODS
Community dwelling individuals with SZ (N=161) or BD (N=130) were administered neuropsychological tests, symptom measures, performance-based social and adaptive (i.e., everyday-living skills) functional competence measures, and rated on domains of real-world functioning: 1) Community and Household activities, 2) Work skills, and 3) Interpersonal relationships. We used confirmatory path analysis to find the best fitting models to examine the direct and indirect (as mediated by competence) prediction of the three domains of real-world functioning.
RESULTS
In all models for both groups, neurocognition’s relationship with outcomes was largely mediated by competence. Symptoms were negatively associated with outcomes but unassociated with competence, with the exception of depression, which was a direct and mediated (through social competence) predictor in BD. In both groups, neurocognition was related to Activities directly and through a mediated relationship with adaptive competence. Work Skills were directly and indirectly (through mediation with social competence) predicted by neurocognition in SZ and entirely mediated by adaptive and social competence in BD. Neurocognition was associated with Interpersonal Relationships directly in the SZ group, and mediated by social competence in both groups.
CONCLUSIONS
Although there was greater disability in SZ, neurocognition predicted worse functioning in all outcome domains in both disorders. Our study supports the shared role of neurocognition in BD and SZ in producing disability, with predictive differences between disorders observed in domain-specific effects of symptoms and social and adaptive competence.
doi:10.1176/appi.ajp.2010.09101406
PMCID: PMC3694770  PMID: 20478878
2.  Linkage analysis of plasma dopamine β-hydroxylase activity in families of patients with schizophrenia 
Human genetics  2011;130(5):635-643.
Dopamine β-hydroxylase (DβH) catalyzes the conversion of dopamine to norepinephrine. DβH enters the plasma after vesicular release from sympathetic neurons and the adrenal medulla. Plasma DβH activity (pDβH) varies widely among individuals, and genetic inheritance regulates that variation. Linkage studies suggested strong linkage of pDβH to ABO on 9q34, and positive evidence for linkage to the complement fixation locus on 19p13.2-13.3. Subsequent association studies strongly supported DBH, which maps adjacent to ABO, as the locus regulating a large proportion of the heritable variation in pDβH. Prior studies have suggested that variation in pDβH, or genetic variants at DβH, associate with differences in expression of psychotic symptoms in patients with schizophrenia and other idiopathic or drug-induced brain disorders, suggesting that DBH might be a genetic modifier of psychotic symptoms. As a first step toward investigating that hypothesis, we performed linkage analysis on pDβH in patients with schizophrenia and their relatives. The results strongly confirm linkage of markers at DBH to pDβH under several models (maximum multipoint LOD score, 6.33), but find no evidence to support linkage anywhere on chromosome 19. Accounting for the contributions to the linkage signal of three SNPs at DBH, rs1611115, rs1611122, and rs6271 reduced but did not eliminate the linkage peak, whereas accounting for all SNPs near DBH eliminated the signal entirely. Analysis of markers genome-wide uncovered positive evidence for linkage between markers at chromosome 20p12 (multi-point LOD = 3.1 at 27.2 cM). The present results provide the first direct evidence for linkage between DBH and pDβH, suggest that rs1611115, rs1611122, rs6271 and additional unidentified variants at or near DBH contribute to the genetic regulation of pDβH, and suggest that a locus near 20p12 also influences pDβH.
doi:10.1007/s00439-011-0989-6
PMCID: PMC3193571  PMID: 21509519
3.  Sensitivity and Specificity of the UCSD Performance-based Skills Assessment (UPSA-B) for Identifying Functional Milestones in Schizophrenia 
Schizophrenia research  2011;132(2-3):165-170.
Schizophrenia is a highly debilitating illness that often results in disruption to independent living and employment. However, “gold standard” methods of assessing functional abilities to achieve these milestones are still lacking. In a sample of 367 individuals with schizophrenia, we examined the sensitivity and specificity of the Brief UCSD Performance-based Skills Assessment (UPSA-B) to predict both residential and employment status. Of all individuals residing independently, 75.9% scored 78 or above on the UPSA-B, and of all individuals not residing independently, 59% scored below 78 on the UPSA-B. Of individuals who were employed, 73.9% scored above 82 on the UPSA-B, and of those not employed, 57.8% scored below 82. These results expand upon both the population base and functional milestones with which the UPSA-B is validated, although future work should examine whether the UPSA-B can be used as a decision aid in the likelihood of success in a longitudinal study, such as at critical transitions (post-hospitalization, cessation of supported housing).
doi:10.1016/j.schres.2011.07.022
PMCID: PMC3195873  PMID: 21843926
Psychosis; Functional Capacity; Functioning; Employment; Independence; Well-being
4.  Replication of an association of a common variant in the Reelin gene (RELN) with schizophrenia in Ashkenazi Jewish women 
Psychiatric genetics  2010;20(4):184-186.
A single nucleotide polymorphism (rs7341475) in RELN has recently been shown to be associated with schizophrenia (SZ) in an Ashkenazi Jewish (AJ) case-control study specifically in women by Shifmen et al. We have replicated this association in women in another large independent AJ collection (721 cases, 259 female; 1455 controls, 834 female) and confirmed that it applies to both SZ and schizoaffective disorder. Further, we explore the effects of this polymorphism through quantitative trait loci (QTL) analysis of 9 SZ related factors providing information on sex-specific genotype-phenotype correlations.
doi:10.1097/YPG.0b013e32833a220b
PMCID: PMC2901865  PMID: 20431428
Schizophrenia; Reelin; Association; Endophenotype; Sex-specific; Ashkenazi; Jewish
5.  Relationship of the Brief UCSD Performance-based Skills Assessment (UPSA-B) to multiple indicators of functioning in people with schizophrenia and bipolar disorder 
Bipolar disorders  2010;12(1):45-55.
Objective
This study assessed the relationship between multiple indicators of ‘real-world’ functioning and scores on a brief performance-based measure of functional capacity known as the Brief University of California San Diego (UCSD) Performance-based Skills Assessment (UPSA-B) in a sample of 205 patients with either serious bipolar disorder (n = 89) or schizophrenia (n = 116).
Methods
Participants were administered the UPSA-B and assessed on the following functional domains: (i) independent living status (e.g., residing independently as head of household, living in residential care facility); (ii) informant reports of functioning (e.g., work skills, daily living skills); (iii) educational attainment and estimated premorbid IQ as measured by years of education and Wide Range Achievement Test reading scores, respectively; and (iv) employment.
Results
Better scores on the UPSA-B were associated with greater residential independence after controlling for age, diagnosis, and symptoms of psychopathology. Among both bipolar disorder and schizophrenia patients, higher UPSA-B scores were significantly related to better informant reports of functioning in daily living skills and work skills domains. Greater estimated premorbid IQ was associated with higher scores on the UPSA-B for both schizophrenia and bipolar disorder participants. Participants who were employed scored higher on the UPSA-B when controlling for age and diagnosis, but not when controlling for symptoms of psychopathology.
Conclusions
These data suggest the UPSA-B may be useful for assessing capacity for functioning in a number of domains in both people diagnosed with schizophrenia and bipolar disorder.
doi:10.1111/j.1399-5618.2009.00787.x
PMCID: PMC2846793  PMID: 20148866
employment; functional capacity; functional outcome; independence; severe; mental illness

Results 1-5 (5)