Improved cognitive content endures for 2 years among unstable responders to acute-phase cognitive therapy for recurrent major depressive disorder.

BACKGROUND: The cognitive model of depression suggests that cognitive therapy (CT) improves major depressive disorder (MDD) in part by changing depressive cognitive content (e.g. dysfunctional attitudes, hopelessness). The current analyses clarified: (1) the durability of improvements in cognitive content made by acute-phase CT responders; (2) whether continuation-phase CT (C-CT) or fluoxetine (FLX) further improves cognitive content; and (3) the extent to which cognitive content mediates continuation treatments' effects on depressive symptoms and major depressive relapse/recurrence. METHOD: Out-patients with recurrent MDD who responded to acute-phase CT (n = 241) were randomized to 8 months of C-CT, FLX or pill placebo (PBO) and followed for an 24 additional months. Cognitive content was assessed approximately every 4 months using five standard patient-report measures. RESULTS: Large improvements in cognitive content made during acute-phase CT were maintained for 32 months, with 78-90% of patients scoring in normal ranges, on average. Cognitive content varied little between C-CT, FLX and PBO arms, overall. Small, transient improvements in cognitive content in C-CT or FLX compared with PBO patients did not clearly mediate the treatments' effects on depressive symptoms or on major depressive relapse/recurrence. CONCLUSIONS: Outpatients with recurrent MDD who respond to acute-phase CT show durable improvements in cognitive content. C-CT or FLX may not continue to improve patient-reported cognitive content substantively, and thus may treat recurrent MDD by other paths.

Association of DLA-DQB1 alleles with exocrine pancreatic insufficiency in Pembroke Welsh Corgis.

Exocrine pancreatic insufficiency (EPI) is a digestive disorder resulting from the insufficient secretion of enzymes from the pancreas. In dogs, this condition is often attributed to pancreatic acinar atrophy, wherein the enzyme-producing acinar cells are believed to be destroyed through an autoimmune process. Although EPI affects many diverse breeds, to date, molecular studies have been limited to the German Shepherd dog. A recent study of major histocompatibility genes in diseased and healthy German Shepherd dogs identified both risk and protective haplotypes. Herein, we genotyped DLA-DQB1 in Pembroke Welsh Corgis to determine whether dog leukocyte antigen alleles contribute to the pathogenesis of EPI across dog breeds. We evaluated 14 affected and 43 control Pembroke Welsh Corgis, which were selected based on an age of onset similar to German Shepherd dogs. We identified one protective allele (odds ratio = 0.13, P-value = 0.044) and one risk allele (odds ratio = 3.8, P-value = 0.047). As in German Shepherd dogs, the risk allele is a duplication of DLA-DQB1 (alleles DQB1*013:03 and 017:01); however, Pembroke Welsh Corgis have acquired a single polymorphism on DQB1*017:01. Thus, the DLA-DQB1 duplication is a risk allele for EPI in at least two breeds.

Change in psychosocial functioning and depressive symptoms during acute-phase cognitive therapy for depression.

BACKGROUND: Major depressive disorder (MDD) is highly prevalent, is recurrent, and impairs people's work, relationships and leisure. Acute-phase treatments improve psychosocial impairment associated with MDD, but how these improvements occur is unclear. In this study, we tested the hypotheses that reductions in depressive symptoms exceed, precede and predict improvements in psychosocial functioning. METHOD: Patients with recurrent MDD (n=523; 68% women, 81% Caucasian, mean age 42 years) received acute-phase cognitive therapy (CT). We measured functioning and symptom severity with the Social Adjustment Scale - Self-Report (SAS-SR), Range of Impaired Functioning Tool (RIFT), Beck Depression Inventory (BDI), Hamilton Rating Scale for Depression (HAMD) and Inventory for Depressive Symptomatology - Self-Report (IDS-SR). We tested cross-lagged correlations between functioning and symptoms measured at baseline and the beginning, middle and end of acute-phase CT. RESULTS: Pre- to post-treatment improvement in psychosocial functioning and depressive symptoms was large and intercorrelated. Depressive symptoms improved more and sooner than did psychosocial functioning. However, among four assessments across the course of treatment, improvements in functioning more strongly predicted later improvement in symptoms than vice versa. CONCLUSIONS: Improvements in psychosocial functioning and depressive symptoms correlate substantially during acute-phase CT, and improvements in functioning may play a role in subsequent symptom reduction during acute-phase CT.

Contrasting prototypes and dimensions in the classification of personality pathology: evidence that dimensions, but not prototypes, are robust.

BACKGROUND: DSM-5 may mark the shift from a categorical classification of personality pathology to a dimensional system. Although dimensional and categorical conceptualizations of personality pathology are often viewed as competing, it is possible to develop categories (prototypes) from combinations of dimensions. Robust prototypes could bridge dimensions and categories within a single classification system. METHOD: To explore prototype structure and robustness, we used finite mixture modeling to identify empirically derived personality pathology prototypes within a large sample (n=8690) of individuals from four settings (clinical, college, community, and military), assessed using a dimensional measure of normal and abnormal personality traits, the Schedule for Nonadaptive and Adaptive Personality (SNAP). We then examined patterns of convergent and discriminant external validity for prototypes. Finally, we investigated the robustness of the dimensional structure of personality pathology. RESULTS: The resulting prototypes were meaningful (externally valid) but non-robust (sample dependent). By contrast, factor analysis revealed that the dimensional structures underlying specific traits were highly robust across samples. CONCLUSIONS: We interpret these results as further evidence of the fundamentally dimensional nature of an empirically based classification of personality pathology.

Age-group differences in facets of positive and negative affect.

OBJECTIVES: The higher order structure of Positive Affect (PA) and Negative Affect (NA) is comparable in self-report affect data from younger and older adults. The current study advances this work by comparing the factor structure of facets of PA and NA in older and younger adults using exploratory and confirmatory factor analyses. METHOD: Older (N = 203; M age = 73.5 years, range 65-92) and younger (N = 349; M age = 19.1 years, range 18-30) adults completed the Positive and Negative Affect Schedule-Expanded Form (PANAS-X) (Watson, D., & Clark, L.A. (1999). Manual for the Positive and Negative Affect Schedule -- Expanded Form. Iowa City, IA: The University of Iowa), which measures General PA and NA as well as three facets of PA (Joviality, Self-Assurance, and Attentiveness) and four facets of NA (Fear, Sadness, Guilt, and Hostility). RESULTS: Item-level exploratory factor analyses of the facet scales revealed structures that were similar in older and younger adults; however, older adult solutions were more diffuse and diverged more from the PANAS-X scale structure. The facet of Sadness exhibited the largest age-group difference, relating more to guilt and anxiety in older than younger adults. CONCLUSION: Older adults may discriminate less amongst specific affect terms or may experience greater affective heterogeneity. Further, Sadness may manifest in age-specific ways. The construct variance of Sadness, and how this issue might be related to the assessment of depression in older adults, is discussed.

Comparison of a Multi-Component Physical Function Battery to Usual Walking Speed for Assessing Lower Extremity Function and Mobility Limitation in Older Adults.

OBJECTIVES: To compare a composite measure of physical function that comprises locomotor and non-locomotor tests (i.e., the Mobility Battery Assessment (MBA)) with traditional measures of mobility (4-m usual gait speed (UGS), six-minute walk (6MW) gait speed, and short physical performance battery (SPPB) score) for assessing lower extremity function and discriminating community dwelling older adults with and without mobility limitations. DESIGN: Cross-sectional, observational study. SETTING: Laboratory-based. PARTICIPANTS: 89 community-dwelling older adults (74.9±6.7). MEASUREMENTS: Using principal component analysis we derived an MBA score for 89 community-dwelling older adults, and quantified 4-m UGS, 6MW gait speed, and SPPB score. The MBA score was based on five lab-based tests. We also quantified self-reported lower extremity function/mobility using the Neuro-QOL Lower Extremity Function-Mobility instrument. Based on this data a continuous score was derived and subjects were classified as "mobility limited" or "non-mobility limited". Correlations between the mobility measures and the Neuro-QOL score were calculated, and ROC curves were constructed to determine the AUC for the mobility measures ability to predict mobility limitations. RESULTS: The MBA had the largest AUC (0.92) for discriminating mobility limitations and exhibited the strongest correlation (0.73) with the Neuro-QOL Lower Extremity Function-Mobility Scale. The worst performing predictors were the 4-meter UGS and stair climb power both with an AUC of 0.8 for discriminating mobility limitations, and a low correlation with Neuro-QOL Lower Extremity Function Scale of 0.39 and 0.46, respectively. CONCLUSION: The MBA score moderately improves the magnitude of correlation and discrimination of mobility limitation in older adults than singular, standard tests of mobility.

Prevalence of deafness in dogs heterozygous or homozygous for the merle allele.

BACKGROUND: Deafness in dogs is frequently associated with the pigment genes piebald and merle. Little is known about the prevalence of deafness in dogs carrying the merle allele. OBJECTIVE: To determine the prevalence of deafness in dogs heterozygous and homozygous for the merle allele of the mouse Silver pigment locus homolog (SILV) gene. ANIMALS: One hundred and fifty-three privately owned merle dogs of different breeds and both sexes. METHODS: Hearing was tested by brainstem auditory-evoked response and classified as bilaterally hearing, unilaterally deaf, or bilaterally deaf. DNA from buccal cells was genotyped as either heterozygous or homozygous for the merle allele. Deafness association tests among merle genotype, eye color, and sex were performed by the chi(2) test. RESULTS: Deafness prevalence in merles overall was 4.6% unilaterally deaf and 4.6% bilaterally deaf. There was a significant association between hearing status and heterozygous versus homozygous merle genotype. For single merles (Mm), 2.7% were unilaterally deaf and 0.9% were bilaterally deaf. For double merles (MM), 10% were unilaterally deaf and 15% were bilaterally deaf. There was no significant association with eye color or sex. CONCLUSIONS: Deafness prevalence in merle dogs was greater than that in some dog breeds homozygous for the piebald gene, such as the English Cocker Spaniel, but comparable to, or lower than, that in the Dalmatian and white Bull Terrier. Dogs homozygous for the merle allele were significantly more likely to be deaf than heterozygotes.

Cost-effectiveness of angiotensin-converting enzyme inhibitors versus angiotensin II receptor blockers as first-line treatment in autosomal dominant polycystic kidney disease.

BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is a rare kidney disorder impacting ∼1:2,500 individuals among the general US population. Hypertension is a significant predictor of ADPKD progression, and a risk factor for development of cardiovascular disease (CVD), the most common cause for mortality among ADPKD patients. Angiotensin-converting enzymes inhibitors (ACE-I) are widely used as first-line treatment in ADPKD for the management of hypertension. However, their cost-effectiveness relative to other hypertensive medications, such as angiotensin II receptor blockers (ARB), has never been assessed. OBJECTIVE: To determine if ARB are more cost-effective than ACE-Is as first-line treatment in ADPKD. METHODS: A Markov-state decision model was constructed for estimation of cost and outcome benefits in hypertensive ADPKD patients. Transition probabilities were extrapolated from a retrospective cohort study comparing chronic kidney disease (CKD) stage transitions in ADPKD patients. Annual pharmaceutical costs per average daily dose per CKD stage were extracted from a US healthcare claims database. Median total healthcare costs per CKD stage or transplant were extracted from the published literature. The time horizon was set to 30 years, with 1-year duration to cycle shift. A cost-effectiveness analysis was conducted to estimate the incremental cost-effectiveness ratio (ICER) of ACE-I vs ARB per additional year of prevented transplant and/or death. A one-way probabilistic sensitivity analysis was conducted, with 10% variation in probabilities and cost. RESULTS: Total annual healthcare costs accrued after 30 years among ADPKD patients taking ACE-Is was estimated to be $3,505,028.41, compared to ARB at $3,644,327.65. Life expectancy was increased by 1.39 years among patients taking ACE-I. Approximate 10-year survival in patients taking ACE-Is was 47% compared to ARB at 34%. CONCLUSIONS: ACE-I dominated ARB and displayed greater cost-effectiveness due to lower cost and increased capacity to prolong years of life without transplant or death among hypertensive ADPKD patients. This model strengthens the value of ACE-I over ARB as first-line treatment for hypertension management in ADPKD patients.

Toward DSM-V and the classification of psychopathology.

The Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) developed by the American Psychiatric Association (1994) is a compelling effort at a best approximation to date of a scientifically based nomenclature, but even its authors have acknowledged that its diagnoses and criterion sets are highly debatable. Well-meaning clinicians, theorists, and researchers could find some basis for fault in virtually every sentence, due in part to the absence of adequate research to guide its construction. Some points of disagreement, however, are more fundamental than others. The authors discuss issues that cut across individual diagnostic categories and that should receive particular attention in DSM-V: (a) the process by which the diagnostic manual is developed, (b) the differentiation from normal psychological functioning, (c) the differentiation among diagnostic categories, (d) cross-sectional vs. longitudinal diagnoses, and (e) the role of laboratory instruments.

Digging up the canine genome--a tale to wag about.

There is incredible morphological and behavioral diversity among the hundreds of breeds of the domestic dog, CANIS FAMILIARIS. Many of these breeds have come into existence within the last few hundred years. While there are obvious phenotypic differences among breeds, there is marked interbreed genetic homogeneity. Thus, study of canine genetics and genomics is of importance to comparative genomics, evolutionary biology and study of human hereditary diseases. The most recent version of the map of the canine genome is comprised of 3,270 markers mapped to 3,021 unique positions with an average intermarker distance of approximately 1 Mb. The markers include approximately 1,600 microsatellite markers, about 1,000 gene-based markers, and almost 700 bacterial artificial chromosome-end markers. Importantly, integration of radiation hybrid and linkage maps has greatly enhanced the utility of the map. Additionally, mapping the genome has led directly to characterization of microsatellite markers ideal for whole genome linkage scans. Thus, workers are now able to exploit the canine genome for a wide variety of genetic studies. Finally, the decision to sequence the canine genome highlights the dog's evolutionary and physiologic position between the mouse and human and its importance as a model for study of mammalian genetics and human hereditary diseases.

Opsonic activity of intravenous immunoglobulin preparations against Staphylococcus epidermidis.

Peritoneal dialysis effluent collected from patients undergoing continuous ambulatory peritoneal dialysis had no opsonic activity against Staphylococcus epidermidis and contained low concentrations of IgG and C3 (roughly equal to those found in 0.5% normal human serum). An intravenous immunoglobulin preparation that showed no opsonic activity against the same organism, on its own or when added to balanced salt solution or peritoneal dialysis fluid, showed good activity when combined with peritoneal dialysis effluent. This was probably due to the presence of low concentrations of C3 in the effluent as prior heat inactivation at 56 degrees C for 30 minutes eliminated any opsonic activity in the immunoglobulin-dialysis effluent mixture. Examination of a range of immunoglobulin preparations showed that their opsonic activity for S epidermidis in the absence of complement varied considerably. Luminol dependent chemiluminescence was unsatisfactory as a method for detecting complement independent immunoglobulin mediated opsonisation. Intravenous immunoglobulin preparations may be useful in boosting the peritoneal defences of those patients undergoing continuous ambulatory peritoneal dialysis (CAPD) who suffer from repeated intraperitoneal infections.

Opsonic requirements of Staphylococcus epidermidis.

The opsonic requirements of 18 strains of Staphylococcus epidermidis were compared in pooled normal human serum and in peritoneal dialysate from patients undergoing continuous ambulatory peritoneal dialysis (CAPD). A serum concentration of 2.5% gave optimal opsonisation. The opsonisation of all strains was antibody- and complement-dependent, and there were no significant differences in the pattern of their opsonic requirements. Peritoneal-dialysis effluent from uninfected patients was a poor source of opsonins because of the low levels of immunoglobulin G and of the C3 component of complement it contained. Growth of S. epidermidis in peritoneal-dialysis effluent rather than in broth did not alter its opsonic requirements. Strains from patients undergoing CAPD and suffering from peritonitis were not more resistant to opsonisation and phagocytic killing than those from other sources.

Introduction to the special section on the concept of disorder.

Despite the absence of a consensual definition of disorder, considerable research and clinical work is based on the categorization and diagnosis of mental disorder. This article introduces a special section of the Journal of Abnormal Psychology that expands the debate between J. C. Wakefield (1999), who has proposed a "harmful dysfunction" analysis of disorder and S. O. Lilienfeld and L. Marino (1995, 1999), who offer an alternative "Roschian" or prototype analysis. This introduction summarizes the main arguments of Wakefield's target article and 8 critiques and discusses the conceptual value of the debate, especially an integration of diverse viewpoints and stimulation to further consideration of this important topic.

Tripartite model of anxiety and depression: psychometric evidence and taxonomic implications.

We review psychometric and other evidence relevant to mixed anxiety-depression. Properties of anxiety and depression measures, including the convergent and discriminant validity of self- and clinical ratings, and interrater reliability, are examined in patient and normal samples. Results suggest that anxiety and depression can be reliably and validly assessed; moreover, although these disorders share a substantial component of general affective distress, they can be differentiated on the basis of factors specific to each syndrome. We also review evidence for these specific factors, examining the influence of context and scale content on ratings, factor analytic studies, and the role of low positive affect in depression. With these data, we argue for a tripartite structure consisting of general distress, physiological hyperarousal (specific anxiety), and anhedonia (specific depression), and we propose a diagnosis of mixed anxiety-depression.

Temperament, personality, and the mood and anxiety disorders.

Literature on temperament, personality, and mood and anxiety disorders is reviewed. The review is organized primarily around L. A. Clark and D. Watson's (1991b) tripartite model for these disorders, but other influential approaches are also examined. Negative affectivity (or neuroticism) appears to be a vulnerability factor for the development of anxiety and depression, indicates poor prognosis, and is itself affected by the experience of disorder. Positive affectivity (or extraversion) is related more specifically to depression, may be a risk factor for its development, suggests poor prognosis, and also may be affected by the experience of disorder. Other personality dimensions (e.g., anxiety sensitivity, attributional style, sociotropy or dependence, autonomy or self-criticism, and constraint) may constitute specific vulnerability factors for particular disorders. More longitudinal and measurement-based research that jointly examines anxiety and depression is needed.

Structures of personality and their relevance to psychopathology.

Trait concepts are used extensively in psychopathology research, but much of this research has failed to consider recent advances in the dimensional structure of personality. Many investigators have discounted the importance of this structural research, arguing that (a) little progress has been made in this area, (b) structural models have little direct relevance for psychopathology research, and (c) the principal methodological tool of structural research--factor analysis--is too subjective to yield psychologically meaningful results. We dispute each of these objections. Specifically, we offer an integrative hierarchical model--composed of four higher order traits--that is congruent with each of the major structural subtraditions within personality. We also discuss the implications of this integrative scheme for basic trait research, for the conceptualization and assessment of psychopathology, and for the etiology of disorder.

Testing a tripartite model: II. Exploring the symptom structure of anxiety and depression in student, adult, and patient samples.

L. A. Clark and D. Watson (1991) proposed a tripartite model of depression and anxiety that divides symptoms into 3 groups: symptoms of general distress that are largely nonspecific, manifestations of anhedonia and low positive affect that are specific to depression, and symptoms of somatic arousal that are relatively unique to anxiety. This model was tested by conducting separate factor analyses of the 90 items in the Mood and Anxiety Symptom Questionnaire (D. Watson & L. A. Clark, 1991) in 5 samples (3 student, 1 adult, 1 patient). The same 3 factors (General Distress, Anhedonia vs. Positive Affect, Somatic Anxiety) emerged in each data set, suggesting that the symptom structure in this domain is highly convergent across diverse samples. Moreover, these factors broadly corresponded to the symptom groups proposed by the tripartite model. Inspection of the individual item loadings suggested some refinements to the model.

Testing a tripartite model: I. Evaluating the convergent and discriminant validity of anxiety and depression symptom scales.

L.A. Clark and D. Watson (1991) proposed a tripartite model that groups symptoms of depression and anxiety into 3 subtypes: symptoms of general distress that are largely nonspecific, manifestations of somatic tension and arousal that are relatively unique to anxiety, and symptoms of anhedonia and low Positive Affect that are specific to depression. This model was tested in 5 samples (3 student, 1 adult, and 1 patient sample) using the Mood and Anxiety Symptom Questionnaire (MASQ; D. Watson & L. A. Clark, 1991), which was designed to assess the hypothesized symptom groups, together with other symptom and cognition measures. Consistent with the tripartite model, the MASQ Anxious Arousal and Anhedonic Depression scales both differentiated anxiety and depression well and also showed excellent convergent validity. Thus, differentiation of these constructs can be improved by focusing on symptoms that are relatively unique to each.

Mood and the mundane: relations between daily life events and self-reported mood.

Daily mood ratings and corresponding diary entries were studied to determine relations between common events and two independent mood factors--Positive Affect (PA) and Negative Affect (NA)--in a sample of 18 young adults over a 3-month period. In an extension of findings from earlier interindividual studies, PA (enthusiastic, delighted vs. sluggish, drowsy) was found to be associated with a wide range of daily events, whereas fewer correlations were found between these events and NA (distressed, nervous, angry vs. calm, relaxed). The relation between high PA and reported social interactions (particularly physically active social events) was especially robust, and its effects were noted repeatedly; NA was unrelated to social activity. As hypothesized, high NA was associated with physical problems; contrary to expectations, low PA also tended to be correlated with health complaints. Overall, the results reaffirm the importance of assessing NA and PA independently and suggest that PA is an interesting and important dimension that deserves more research attention. Theoretical considerations and clinical implications are discussed.

Development and validation of brief measures of positive and negative affect: the PANAS scales.

In recent studies of the structure of affect, positive and negative affect have consistently emerged as two dominant and relatively independent dimensions. A number of mood scales have been created to measure these factors; however, many existing measures are inadequate, showing low reliability or poor convergent or discriminant validity. To fill the need for reliable and valid Positive Affect and Negative Affect scales that are also brief and easy to administer, we developed two 10-item mood scales that comprise the Positive and Negative Affect Schedule (PANAS). The scales are shown to be highly internally consistent, largely uncorrelated, and stable at appropriate levels over a 2-month time period. Normative data and factorial and external evidence of convergent and discriminant validity for the scales are also presented.