Psychotherapy for personality disorders: Questions of clinical utility.

Patients with personality disorders (PDs) represent a particular burden for the health system and the clinicians attempting to treat them. The current commentary complements reviews of outcome studies on treatments for PDs by focusing on the clinical utility as defined by the American Psychological Association. As such, extending that notion, clinical utility of a treatment comprises aspects of implementation and training in the model as well as qualities of the therapeutic technique and relationship. Our review suggests that a certain caution needs to be applied when reading outcome studies based on specific methodological caveats. In specific contexts, inpatient and day hospital treatments have some initial appeal in reducing symptoms, in particular for the treatment of more severe forms of Cluster A and B PDs. In general, treatments for PDs are long-term treatments, administered in rather high dosage, which tends to be true irrespective of the treatment model. For specific treatment targets, there is emerging evidence on effectiveness of short-term interventions. The therapeutic relationship with patients with PDs may be characterized by strains and interactional difficulties that may be addressed using clinically adapted treatment strategies. To be effective, therapists should have an open-minded and flexible approach to therapy, which is particularly central from an integrative perspective. Finally, we state that a key element for implementation of an effective treatment model is a manual-based training that, albeit controversial, remains a key component allowing for the trainee therapist to self-monitor his or her progress and get specific help in supervision as part of the learning process. We advocate that clinicians and administrators should consider these points as being specifically related with clinical utility of treatments for PDs because they contribute to optimize the implementation process of a therapy approach to a specific context

Apego como marco teórico para entender los trastornos de personalidad: Consideraciones psicoterapéuticas, neurocientíficas y de desarrollo

In this paper we propose that John Bowlby\u27s attachment theory provides a theoretically coherent, empirically based, and clinically useful model for understanding personality pathology. This theoretical framework brings parsimony and breadth to the conceptualization of the etiology, maintenance, and treatment of personality disorders (PDs). Attachment theory can explain both the intrapersonal and interpersonal difficulties common in those with PDs and is consistent with findings from studies across multiple domains of knowledge, including evolutionary biology, ethology/comparative psychology, developmental psychology, experimental social-personality psychology, and neuroscience.PDs are characterized by significant interpersonal challenges. Recently, these challenges have been hypothesized to stem from underlying maladaptive attachment schemas. Our goal is to outline and elaborate on attachment theory as a foundation for the etiology and pathology of PDs and to highlight the implications of this theory for treatment. We begin with a brief review of attachment, describing its conceptualization and assessment in both children and adults in order to examine PD development. This theoretical foundation is supported by a body of empirical research, from which we present findings from neurobiological and developmental literatures linking attachment and PDs. We then examine the role of attachment in the psychotherapy process and in treatment outcome. Further, we outline research reporting changes in attachment patterns as a result of treatment. Finally, we summarize the implications of attachment theory for understanding PDs and present possible directions for future research.En este trabajo proponemos que la teoría de apego de John Bowlby ofrece un modelo teoréticamente coherente, empíricamente basado y clínicamente útil para entender la patología de personalidad. Este marco teorético trae parquedad y anchura a la conceptualización de la etiología, mantenimiento y tratamiento de trastornos de personalidad. La teoría de apego puede explicar las dificultades tanto intrapersonales como interpersonales comunes a las personas con trastornos de personalidad y es consistente con los descubrimientos de estudios de varios dominios del saber, incluyendo biología evolutiva, etiología/psicología comparada, psicología de desarrollo, psicología de personalidad y psicología social-personalidad experimental, y neurociencia. Trastornos de personalidad son caracterizados por los retos interpersonales significativos. Últimamente, se han hecho hipótesis que estos retos son el resultado de esquemas de apego mal adaptivos. Nuestro objetivo es explicar y elaborar la teoría de apego como la base para la etiología y patología de trastornos de personalidad y acentuar las implicaciones de esta teoría para el tratamiento. Empezamos con un pequeño análisis del apego, describiendo sus conceptualizaciones y evaluación tanto en niños como adultos para examinar el desarrollo de trastornos de personalidad. Este fundamento teórico está apoyado por la investigación empírica, de la que presentamos resultados de la literatura neurobiológica y de desarrollo relacionados con el apego y los trastornos de personalidad. Luego investigamos el papel que tiene el apego en los procesos de psicoterapia y en los resultados del tratamiento. Finalmente, resumimos las implicaciones de la teoría de apego para entender trastornos de personalidad y presentamos unas posibles direcciones para las futuras investigaciones

The Changing Nature of Poverty

Since the beginning of the War on Poverty, the poverty rate has fluctuated widely, and at the same time the poverty population has undergone many changes, some mirroring the changing stereotypes of the poor and others less pronounced than the changing stereotypes would lead us to believe. A feminization of poverty has occurred, with many more of the poor now in households headed by women. Interestingly, aging of the poverty population has not occurred despite growth in the elderly segment of the overall population. Concerning turnover in the poverty population, we find that despite poverty theories emphasizing persistence, recurrent poverty is relatively rare and poverty is not generally passed from one generation to the next. Poverty prevention has come from both economic growth and government transfers; however, inequality in economic growth has contributed to poverty. With the proportion of elderly and female- headed households likely to continue at a high level into the future, poverty rates are also likely to remain high unless government transfers are increased.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/66979/2/10.1177_000271628547900103.pd

Attachment and Mentalization in Female Patients With Comorbid Narcissistic and Borderline Personality Disorder

We investigated attachment representations and the capacity for mentalization in a sample of adult female borderline patients with and without comorbid narcissistic personality disorder (NPD). Participants were 22 borderline patients diagnosed with comorbid NPD (NPD/BPD) and 129 BPD patients without NPD (BPD) from 2 randomized clinical trials. Attachment and mentalization were assessed on the Adult Attachment Interview (AAI; George

Report of New Haplotype for ABCC2 Gene rs17222723 and rs8187718 in cis

The ATP-binding cassette, subfamily C [CFTR/MRP], member 2 (ABCC2) gene is a member of the ATP-binding cassette transporters and is involved in the transport of molecules across cellular membranes. Substrates transported by ABCC2 include antiepileptics, statins, tenofovir, cisplatin, irinotecan, and carbamazepine. Because of the pharmacogenomics implications, we developed a clinical laboratoryedeveloped assay to test for seven variants in the ABCC2 gene: c.3563T>A (p.V1188E, rs17222723), c.1249G>A (p.V417I, rs2273697), c.3972C>T (p.I1324I, rs3740066), c.2302C>T (p.R768W, rs56199535), c.2366C>T (p.S789F, rs56220353), c.-24C>T (50 UTR, rs717620), and c.4544G>A (p.C1515Y, rs8187710). During the validation process, we noted several DNA samples, obtained from the Coriell Cell Repository, that contained both c.3563T>A, c.4544G>A, and a third variant, suggesting that c.3563T>A and c.4544G>A are in cis on the chromosome in some individuals. We obtained DNA samples from a trio (father, mother, and child), tested their ABCC2 variants, and confirmed that c.3563T>A and c.4544G>A were in cis on the same chromosome. Here, we report a new haplotype in ABCC2. (J Mol Diagn 2015, 17: 201e205; http://dx.doi.org/10.1016/ j.jmoldx.2014.11.005

Orthostatic hypotension and novel blood pressure-associated gene variants: Genetics of Postural Hemodynamics (GPH) Consortium

Aims Orthostatic hypotension (OH), an independent predictor of mortality and cardiovascular events, strongly correlates with hypertension. Recent genome-wide studies have identified new loci influencing blood pressure (BP) in populations, but their impact on OH remains unknown. Methods and resultsA total of 38 970 men and women of European ancestry from five population-based cohorts were included, of whom 2656 (6.8) met the diagnostic criteria for OH (systolic/diastolic BP drop <20/10 mmHg within 3 min of standing). Thirty-one recently discovered BP-associated single nucleotide polymorphisms (SNPs) were examined using an additive genetic model and the major allele as referent. Relations between OH, orthostatic systolic BP response, and genetic variants were assessed by inverse variance-weighted meta-analysis. We found Bonferroni adjusted (P < 0.0016) significant evidence for association between OH and the EBF1 locus (rs11953630, per-minor-allele odds ratio, 95 confidence interval: 0.90, 0.850.96; P=0.001), and nominal evidence (P < 0.05) for CYP17A1 (rs11191548: 0.85, 0.750.95; P=0.005), and NPR3-C5orf23 (rs1173771: 0.92, 0.870.98; P=0.009) loci. Among subjects not taking BP-lowering drugs, three SNPs within the NPPA/NPPB locus were nominally associated with increased risk of OH (rs17367504: 1.13, 1.021.24; P=0.02, rs198358: 1.10, 1.011.20; P=0.04, and rs5068: 1.22, 1.041.43; P=0.01). Moreover, an ADM variant was nominally associated with continuous orthostatic systolic BP response in the adjusted model (P=0.04). ConclusionThe overall association between common gene variants in BP loci and OH was generally weak and the direction of effect inconsistent with resting BP findings. These results suggest that OH and resting BP share few genetic components

Identification of microbial DNA in human cancer

<p>Abstract</p> <p>Background</p> <p>Microorganisms have been associated with many types of human diseases; however, a significant number of clinically important microbial pathogens remain to be discovered.</p> <p>Methods</p> <p>We have developed a genome-wide approach, called Digital Karyotyping Microbe Identification (DK-MICROBE), to identify genomic DNA of bacteria and viruses in human disease tissues. This method involves the generation of an experimental DNA tag library through Digital Karyotyping (DK) followed by analysis of the tag sequences for the presence of microbial DNA content using a compiled microbial DNA virtual tag library.</p> <p>Results</p> <p>To validate this technology and to identify pathogens that may be associated with human cancer pathogenesis, we used DK-MICROBE to determine the presence of microbial DNA in 58 human tumor samples, including brain, ovarian, and colorectal cancers. We detected DNA from Human herpesvirus 6 (HHV-6) in a DK library of a colorectal cancer liver metastasis and in normal tissue from the same patient.</p> <p>Conclusion</p> <p>DK-MICROBE can identify previously unknown infectious agents in human tumors, and is now available for further applications for the identification of pathogen DNA in human cancer and other diseases.</p

KCNT1- related epilepsy: An international multicenter cohort of 27 pediatric cases

ObjectiveThrough international collaboration, we evaluated the phenotypic aspects of a multiethnic cohort of KCNT1- related epilepsy and explored genotype- phenotype correlations associated with frequently encountered variants.MethodsA cross- sectional analysis of children harboring pathogenic or likely pathogenic KCNT1 variants was completed. Children with one of the two more common recurrent KCNT1 variants were compared with the rest of the cohort for the presence of particular characteristics.ResultsTwenty- seven children (15 males, mean age = 40.8 months) were included. Seizure onset ranged from 1 day to 6 months, and half (48.1%) exhibited developmental plateauing upon onset. Two- thirds had epilepsy of infancy with migrating focal seizures (EIMFS), and focal tonic seizures were common (48.1%). The most frequent recurrent KCNT1 variants were c.2800G>A; p.Ala934Thr (n = 5) and c.862G>A; p.Gly288Ser (n = 4). De novo variants were found in 96% of tested parents (23/24). Sixty percent had abnormal magnetic resonance imaging (MRI) findings. Delayed myelination, thin corpus callosum, and brain atrophy were the most common. One child had gray- white matter interface indistinctness, suggesting a malformation of cortical development. Several antiepileptic drugs (mean = 7.4/patient) were tried, with no consistent response to any one agent. Eleven tried quinidine; 45% had marked (>50% seizure reduction) or some improvement (25%- 50% seizure reduction). Seven used cannabidiol; 71% experienced marked or some improvement. Fourteen tried diet therapies; 57% had marked or some improvement. When comparing the recurrent variants to the rest of the cohort with respect to developmental trajectory, presence of EIMFS, >500 seizures/mo, abnormal MRI, and treatment response, there were no statistically significant differences. Four patients died (15%), none of sudden unexpected death in epilepsy.SignificanceOur cohort reinforces common aspects of this highly pleiotropic entity. EIMFS manifesting with refractory tonic seizures was the most common. Cannabidiol, diet therapy, and quinidine seem to offer the best chances of seizure reduction, although evidence- based practice is still unavailable.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/154940/1/epi16480_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/154940/2/epi16480.pd

RESCUE OF HIPPO CO-ACTIVATOR YAP1 TRIGGERS DNA DAMAGE-INDUCED APOPTOSIS IN HEMATOLOGICAL CANCERS

Oncogene–induced DNA damage elicits genomic instability in epithelial cancer cells, but apoptosis is blocked through inactivation of the tumor suppressor p53. In hematological cancers, the relevance of ongoing DNA damage and mechanisms by which apoptosis is suppressed are largely unknown. We found pervasive DNA damage in hematologic malignancies including multiple myeloma, lymphoma and leukemia, which leads to activation of a p53–independent, pro-apoptotic network centered on nuclear relocalization of ABL1 kinase. Although nuclear ABL1 triggers cell death through its interaction with the Hippo pathway co–activator YAP1 in normal cells, we show that low YAP1 levels prevent nuclear ABL1–induced apoptosis in these hematologic malignancies. YAP1 is under the control of a serine–threonine kinase, STK4. Importantly, genetic inactivation of STK4 restores YAP1 levels, triggering cell death in vitro and in vivo. Our data therefore identify a novel synthetic–lethal strategy to selectively target cancer cells presenting with endogenous DNA damage and low YAP1 levels