Factors differentiating personality-disordered individuals with and without a history of unipolar mood disorder

The relationship between mood disorders and personality disorders has been of longstanding interest to clinicians. Despite theoretical reasons to do so, virtually no studies have examined factors that discriminate personality-disordered subjects with a history of mood disorder (PD/HMD) from personality-disordered subjects without a history of mood disorder (PD). This study examined demographic variables, patterns of comorbidity, measures of life functioning, personality traits, and early life experiences differentiating PD/HMD (n = 83) from PD (n = 214). Diagnoses were assigned using structured clinical interviews and a best-estimate procedure. The results suggest that subjects with borderline personality disorder are more likely to have a life history of mood disorder than are subjects with other personality disorders. In addition, PD/HMDs are more likely to receive a diagnosis of anxiety disorder or alcoholism, to have lower Global Assessment of Functioning (GAF) scores, and to have sought treatment than PDs. On self-report measures of personality, PD/HMDs endorse higher levels of trait anxiety and affective lability (e.g., Harm Avoidance, Neuroticism) than do PDs. PD/HMDs are also more likely to report childhood physical and emotional abuse than are PDs, and to describe their parents as using affectionless control. No differences were found between Axis II clusters as a function of mood disorder history. The discussion suggests a potential model in which early environmental stress interacts with constitutional vulnerabilities to put individuals at an increased risk for both mood and anxiety disorders as well as personality disorders.     

Distal esophageal ballooning following Heller myotomy

Eccentric ballooning of the distal esophagus was observed radiographically in 11 of 23 patients (48%) who underwent Heller myotomy for achalasia. While, to the authors' knowledge, ballooning at the site of myotomy incision has not been described previously in the radiologic literature, it should be recognized as a normal and frequent postoperative finding. Radiologists should be aware of this finding so that it is not mistaken for postoperative abnormalities following esophagomyotomy or an epiphrenic diverticulum.     

Fibronectin binding to thrombin-stimulated platelets: evidence for fibrin(ogen) independent and dependent pathways

Plasma fibronectin binds in a specific and saturable manner to thrombin- stimulated platelets. gamma-Thrombin stimulated 80% as much fibronectin binding to platelets as alpha-thrombin with conversion of less than or equal to 1% of platelet fibrinogen to fibrin. Afibrinogenemic and normal platelets bound similar quantities of fibronectin in the presence of calcium or magnesium-ethylene glycol tetra-acetic acid (EGTA). These observations indicate that fibronectin can interact with platelets without involvement of fibrin or fibrinogen. Nevertheless, two different effects of fibrin(ogen) on fibronectin binding were observed. First, exogenous fibrinogen inhibited fibronectin binding to thrombin-stimulated platelets. This inhibition was unidirectional, as fibronectin did not inhibit fibrinogen binding to ADP or thrombin- stimulated cells. Second, formaldehyde-fixed cells with surface- associated fibrin bound significant quantities of fibronectin. This interaction required calcium and did not occur on fixed cells with or without surface-bound fibrinogen. A portion of the ligand bound to fixed cells with surface-associated fibrin was modified to form a derivative with a molecular weight identical to that of the fibronectin subunit cross-linked to the alpha-chain of fibrin. This high mol wt derivative was also observed to a variable extent with living cells in the presence of magnesium or calcium but not in the presence of magnesium-EGTA. Thus, fibronectin binds to platelets by at least two mechanisms: (1) a fibrin(ogen)-independent pathway that requires divalent ions and is inhibited by exogenous fibrinogen; and (2) a fibrin-dependent pathway with an absolute calcium requirement. With nonaggregated, thrombin-stimulated platelets, the former pathway appears to predominate.     

Diamond-Blackfan syndrome: evidence against cell-mediated erythropoietic suppression

The profound anemia of Diamond-Blackfan syndrome (DBS) is due to marrow red cell failure, but the pathogenesis is not understood. Studies by others indicated cell-mediated erythropoietic suppression in this condition. To explore this mechanism further, Ficoll-Hypaque--separated peripheral blood lymphocytes (PBL) from four anemic untreated patients with DBS, or from normals were cocultured with control marrow in vitro and the growth of erythropoietin-responsive stem cell colonies (CFU-E) was dermined. CFU-E numbers obtained from cultures with added normal PBL were not significantly different from the number without PBL. Similarly, CFU-E from cultures with added DBS PBL were not significantly different from the number without PBL (215 versus 220, 229 versus 220 and 84 versus 60, 74 versus 94/10(5) cells, respectively). Mixing marrows from a control and one DBS patient in ratios of 2:1, 1:1, or 1:2 prior to culture failed to disclose a decrease of colony growth. We could not show cellular inhibition of erythropoiesis in these patients with DBS. The mechanism of anemia in this disorder remains an open question.     

Multivariate Behavior Genetic Analyses of Aggressive Behavior Subtypes

This study examined the genetic and environmental architecture underlying aggressive behavior measured by the Life History of Aggression Questionnaire (LHA; Coccaro et al. 1997a). Following preliminary phenotypic factor analysis procedures, multivariate behavioral genetics models were fit to responses from 2,925 adult twins from the PennTwins cohort on five LHA items assessing lifetime frequency of temper tantrums, indirect aggression, verbal aggression, fighting, and physical assault. The best-fitting model was a 2-factor common pathway model, indicating that these five aggressive behaviors are underpinned by two distinct etiological factors with different genetic and nonshared environmental influences. Although there was evidence of significant sex differences, the structure of the two factors appeared to be quite similar in males and females, where General Aggression and Physical Aggression factors emerged. Heritability of these factors ranged from .37 to .57, and nonshared environmental effects ranged from .43 to .63. The results of this study highlight the heterogeneous nature of the aggression construct and the need to consider differences in genetic and environmental influences on individual aggressive behaviors in a multivariate context.     

Genomic architecture of aggression: Rare copy number variants in intermittent explosive disorder

Copy number variants (CNVs) are known to be associated with complex neuropsychiatric disorders (e.g., schizophrenia and autism) but have not been explored in the isolated features of aggressive behaviors such as intermittent explosive disorder (IED). IED is characterized by recurrent episodes of aggression in which individuals act impulsively and grossly out of proportion from the involved stressors. Previous studies have identified genetic variants in the serotonergic pathway that play a role in susceptibility to this behavior, but additional contributors have not been identified. Therefore, to further delineate possible genetic influences, we investigated CNVs in individuals diagnosed with IED and/or personality disorder (PD). We carried out array comparative genomic hybridization on 113 samples of individuals with isolated features of IED (n = 90) or PD (n = 23). We detected a recurrent 1.35‐Mbp deletion on chromosome 1q21.1 in one IED subject and a novel ～350‐kbp deletion on chromosome 16q22.3q23.1 in another IED subject. While five recent reports have suggested the involvement of an ～1.6‐Mbp 15q13.3 deletion in individuals with behavioral problems, particularly aggression, we report an absence of such events in our study of individuals specifically selected for aggression. We did, however, detect a smaller ～430‐kbp 15q13.3 duplication containing CHRNA7 in one individual with PD. While these results suggest a possible role for rare CNVs in identifying genes underlying IED or PD, further studies on a large number of well‐characterized individuals are necessary. © 2011 Wiley‐Liss, Inc.     

Overview and update on molecular testing in non-small cell lung carcinoma utilizing endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) samples

Lung carcinoma remains one of the most frequent and aggressive human neoplasms. Fortunately, in the last decades, the increasing knowledge of the molecular mechanisms leading to cancer development has allowed the use of targeted therapies with improvement of prognosis in many patients. Clinical management has also changed after the introduction of endobronchialultrasonographic bronchoscopy that allows a conservative staging of lung tumors, avoiding the need of mediastinoscopy for lymph node staging. Lung pathologists and cytopathologists are facing the challenge of giving the more comprehensive prognostic and predictive information with ever smaller tissue or cytological samples. The aim of this review is to summarize the molecular testing for non-small cell lung carcinoma and how pathologists can contribute to the patient's outcome with a conscious management of biological samples.     

Intermittent explosive disorder: development of integrated research criteria for Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition

This study was designed to develop a revised diagnostic criteria set for intermittent explosive disorder (IED) for consideration for inclusion in Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-V). This revised criteria set was developed by integrating previous research criteria with elements from the current DSM-IV set of diagnostic criteria. Evidence supporting the reliability and validity of IED-IR (“IED Integrated Criteria”) in a new and well-characterized group of subjects with personality disorder is presented. Clinical, phenomenologic, and diagnostic data from 201 individuals with personality disorder were reviewed. All IED diagnoses were assigned using a best-estimate process (eg, kappa for IED-IR >0.85). In addition, subjects meeting IED-IR criteria had higher scores on dimensional measures of aggression and had lower global functioning scores than non–IED-IR subjects, even when related variables were controlled. The IED-IR criteria were more sensitive than the DSM-IV criteria only in identifying subjects with significant impulsive-aggressive behavior by a factor of 16. We conclude that the IED-IR criteria can be reliably applied and have sufficient validity to warrant consideration as DSM-V criteria for IED.     

Relationship between depressive mood and chronotype in healthy subjects

Aim:  The endogenous circadian clock generates daily variations of physiological and behavior functions such as the endogenous interindividual component (morningness/eveningness preferences). Also, mood disorders are associated with a breakdown in the organization of ultradian rhythm. Therefore, the purpose of the present study was to assessed the association between chronotype and the level of depressive symptoms in a healthy sample population. Furthermore, the components of the depression scale that best discriminate the chronotypes were determined.
Methods:  This cross-sectional study involved 200 volunteers, aged 18–99 years, 118 women and 82 men. The instruments were the Montgomery–Äsberg Depression Rating Scale (MADRS), the Morningness/Eveningness Questionnaire, the Self-Reporting Questionnaire-20, and the future self-perception questionnaire.
Results:  Logistic regression showed that subjects with the eveningness chronotype had a higher chance of reporting more severe depressive symptoms compared to morning- and intermediate-chronotypes, with an odds ratio (OR) of 2.83 and 5.01, respectively. Other independent cofactors associated with a higher level of depressive symptoms were female gender (OR, 3.36), minor psychiatric disorders (OR, 3.70) and low future self-perception (OR, 3.11). Younger age, however, was associated with a lower level of depressive symptoms (OR, 0.97). The questions in the MADRS that presented higher discriminate coefficients among chronotypes were those related to sadness, inner tension, sleep reduction and pessimism.
Conclusion:  Identification of an association between evening typology and depressive symptoms in healthy samples may be useful in further investigation of circadian typology and the course of depressive disease.