Thought disorder in the meta-structure of psychopathology.

BACKGROUND: Dimensional models of co-morbidity have the potential to improve the conceptualization of mental disorders in research and clinical work, yet little is known about how relatively uncommon disorders may fit with more common disorders. The present study estimated the meta-structure of psychopathology in the US general population focusing on the placement of five under-studied disorders sharing features of thought disorder: paranoid, schizoid, avoidant and schizotypal personality disorders, and manic episodes as well as bipolar disorder. METHOD: Data were drawn from the National Epidemiologic Survey on Alcohol and Related Conditions, a face-to-face interview of 34 653 non-institutionalized adults in the US general population. The meta-structure of 16 DSM-IV Axis I and Axis II psychiatric disorders, as assessed by the Alcohol Use Disorder and Associated Disabilities Interview Schedule DSM-IV version (AUDADIS-IV), was examined using exploratory and confirmatory factor analysis. RESULTS: We document an empirically derived thought disorder factor that is a subdomain of the internalizing dimension, characterized by schizoid, paranoid, schizotypal and avoidant personality disorders as well as manic episodes. Manic episodes exhibit notable associations with both the distress subdomain of the internalizing dimension as well as the thought disorder subdomain. The structure was replicated for bipolar disorder (I or II) in place of manic episodes. CONCLUSIONS: As our understanding of psychopathological meta-structure expands, incorporation of disorders characterized by detachment and psychoticism grows increasingly important. Disorders characterized by detachment and psychoticism may be well conceptualized, organized and measured as a subdimension of the internalizing spectrum of disorders. Manic episodes and bipolar disorder exhibit substantial co-morbidity across both distress and thought disorder domains of the internalizing dimension. Clinically, these results underscore the potential utility of conceptualizing patient treatment needs using an approach targeting psychopathological systems underlying meta-structural classification rubrics.

Borderline personality disorder co-morbidity: relationship to the internalizing-externalizing structure of common mental disorders.

BACKGROUND: Borderline personality disorder (BPD) shows high levels of co-morbidity with an array of psychiatric disorders. The meaning and causes of this co-morbidity are not fully understood. Our objective was to investigate and clarify the complex co-morbidity of BPD by integrating it into the structure of common mental disorders. METHOD: We conducted exploratory and confirmatory factor analyses on diagnostic interview data from a representative US population-based sample of 34 653 civilian, non-institutionalized individuals aged ≥18 years. We modeled the structure of lifetime DSM-IV diagnoses of BPD and antisocial personality disorder (ASPD), major depressive disorder, dysthymic disorder, panic disorder with agoraphobia, social phobia, specific phobia, generalized anxiety disorder, post-traumatic stress disorder, alcohol dependence, nicotine dependence, marijuana dependence, and any other drug dependence. RESULTS: In both women and men, the internalizing-externalizing structure of common mental disorders captured the co-morbidity among all disorders including BPD. Although BPD was unidimensional in terms of its symptoms, BPD as a disorder showed associations with both the distress subfactor of the internalizing dimension and the externalizing dimension. CONCLUSIONS: The complex patterns of co-morbidity observed with BPD represent connections to other disorders at the level of latent internalizing and externalizing dimensions. BPD is meaningfully connected with liabilities shared with common mental disorders, and these liability dimensions provide a beneficial focus for understanding the co-morbidity, etiology and treatment of BPD.

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.

A mutation allowing expression of normally silent a mating-type information in Saccharomyces cerevisiae.

Mating type in haploid cells of the yeast Saccharomyces cerevisiae is determined by a pair of alleles MATa and MAT alpha. Under various conditions haploid mating types can be interconverted. It has been proposed that transpositions of silent cassettes of mating-type information from HML OR HMR to MAT are the source of mating type conversions. A mutation described in this work, designated AON1, has the following properties. (1) MAT alpha cells carring AON1 are defective in mating. (2) AON1 allows MAT alpha/MAT alpha but not MATa/MATa diploids to sporulate; thus, AON1 mimics the MATa requirement for sporulation. (3) mata-1 cells that carry AON1 are MATa phenocopies, i.e., MAT alpha/mata-1 AON1 diploids behave as standard MAT alpha/MATa cells; therefore, AON1 suppresses the defect of mata-1. (4) AON1 maps at or near HMRa. (5) Same-site revertants from AON1 lose the ability to convert mating type to MATa, indicating that reversion is associated with the loss of a functional HMRa locus. In addition, AON1 is a dominant mutation. We conclude that AON1 is a regulatory mutation, probably cis-acting, that leads to the constitutive expression of silent a mating-type information located at HMRa.

Genetic analysis of multiple drug cross resistance in Saccharomyces cerevisiae: a nuclear-mitochondrial gene interaction.

A mutant of the yeast Saccharomyces cerevisiae, cross resistant to several antibiotics, was isolated in our laboratory and subjected to genetic analysis. Tetrad analysis of diploids obtained from crosses between the resistant mutant and a sensitive wild-type strain suggest that the multiple resistance to the five agents, oligomycin (OLI), rhodamine 6G (RHG), tetracycline (TCN), chloramphenicol (CAP) and cycloheximide (CHX) is determined by a single nuclear gene, ant1, and requires several cytoplasmic genes for expression of resistance to oligomycin, rhodamine 6G and tetracycline. --Vegetatively growing diploid clones derived from the cross ant1 [RHO+] X +[RHO+] show mitotic segregation of two phenotypic classes for the drugs OLI, RHG TCN. Diploids derived from the two reciprocal crosses, ant1 [RHO+] X +[RHO-] and ant1 [RHO-] X +[RHO+], fail to exhibit mitotic segregation. These results are consistent with our hypothesis concerning the involvement of cytoplasmic loci. They suggest, in addition, that these loci are associated with mitochondrial DNA (mtDNA). --Evidence for this association is provided by the demonstration of genetic linkage between the cytoplasmic loci involved in the interaction, RHG-1, TCN-1 and OLI-5, and two well-characterized mitochondrial loci, ERY and CAP. --We have mapped the nuclear ant1 locus 3.3 cM from the centromere-linked gene, leu1, on the same side of the centromere of chromosome VII as leu1. --In the light of these findings, we discuss the claims made by several authors of the episomal nature of mutations similar to the one described here, as well as of the possible involvement of yeast 2 mu DNA in such mutations.

Thermal inactivation of maltase and its application to temperature-sensitive mutants of yeast.

Three maltases have been detected in each of a variety of strains of Saccharomyces. These are present in constant relative amounts in a particular strain and are characterized by reproducible first order thermal decay constants. Four of six mutants, temperature-sensitive for maltose fermentation, lack the maltase of intermediate stability. This deficiency appears to be the basis of the temperature sensitivity, and it is concluded that these strains carry a mutation in the structural gene for that maltase.

Selective inhibition of growth by the proline analogue thiazolidine-4-carboxylic acid and its probable mode of action in Saccharomyces cerevisiae.

Cells of Saccharomyces cerevisiae showed differential growth inhibition when cultured on various carbon sources in the presence of the proline analogue thiazolidine-4-carboxylic acid (TZ). On 0.5% yeast extract, 2% glucose and TZ (10 mg/ml) medium, growth lags from 8 to 10 h were observed, after which cells recovered and growth proceeded normally. Growth was totally inhibited on a medium of 0.5% yeast extract, 3% ethanol, and 5 mg of TZ per ml. This inhibition was not due to the inability of cells to undergo aerobic respiration, since similar media containing glycerol instead of ethanol allowed growth. Proline added to the culture medium reversed the lag on glucose and TZ medium but did not promote recovery on ethanol and TZ medium. TZ was found to have two probable modes of action in yeast. It was a noncompetitive inhibitor of yeast alcohol dehydrogenase, and it was also found to be incorporated into cellular protein. Uptake studies using (14)C-labeled TZ showed that the recovery on glucose was correlated with the progressive exclusion of the analogue from cells.