Forecasting the Future, Remembering the Past: Misrepresentations of daily emotional experience in generalized anxiety disorder and major depressive disorder

Studies have shown that individuals with emotional disorders expect and recall more negative and less positive information than healthy individuals. However, no study of emotional disorders has investigated affective forecasting and affective memory within the same individuals. Using ecological momentary assessment, we compared daily affective experiences to forecasts and memories in 145 adults with generalized anxiety disorder (GAD), major depressive disorder (MDD), comorbid GAD/MDD, or no psychopathology. All three clinical groups forecast, experienced, and remembered more negative affect than controls; positive affect showed the opposite pattern, which was especially robust for the depressed groups. All clinical groups demonstrated stronger negative forecasting and memory biases as well as a weaker positive forecasting bias than controls. However, when the independent contributions of symptom dimensions were analyzed, MDD severity was associated with a negative forecasting bias while GAD severity was associated with a negative memory bias. Cognitive representations of emotional experiences in GAD and MDD are biased in ways that may maintain the disorders and represent promising intervention targets

Restlessness in generalized anxiety disorder: Using actigraphy to measure physiological reactions to threat

Generalized anxiety disorder (GAD) is characterized by excessive, uncontrollable worry accompanied by symptoms of physiological arousal. Although individuals with GAD report greater subjective arousal than healthy individuals, they show equivalent or even attenuated physiological reactions to threat. This may result from using physiological measures better suited to fear than anxiety. To test this possibility, 102 adults with and without GAD were assessed for restlessness, a core physiological symptom of GAD. They were exposed to an in vivo threat task designed to elicit anxiety in the laboratory. Throughout the task, restlessness was measured physiologically with actigraphy sensors on both ankles and both wrists, and subjectively with self-report ratings. The GAD group reported higher subjective restlessness than the no-GAD group, and in the subset of cases who had restlessness as a clinically significant symptom, actigraphy scores were reliably elevated as well. However, although actigraphy scores increased with proximity to the threat, the increases did not differ by group. These findings provide initial validation for actigraphy as a novel measure of motor restlessness in GAD. In addition, they underscore the value of measuring restlessness using multiple assessment methods. These methods suggest that, in GAD, restlessness reflects a chronic state of arousal rather than a heightened physiological reaction to threat

Youth with psychopathy features are not a discrete class: a taxometric analysis

BACKGROUND: Recently, researchers have sought to measure psychopathy-like features among youth in hopes of identifying children who may be progressing toward a particularly destructive form of adult pathology. However, it remains unclear whether psychopathy-like personality features among youth are best conceptualized as dimensional (distributed along a continuum) or taxonic (such that youth with psychopathic personality characteristics are qualitatively distinct from non-psychopathic youth). METHODS: This study applied taxometric analyses (MAMBAC, MAXEIG, and L-Mode) to scores from two primary measures of youth psychopathy features: the Psychopathy Checklist: Youth Version (N = 757) and the self-report Antisocial Process Screening Device (N = 489) among delinquent boys. RESULTS: All analyses supported a dimensional structure, indicating that psychopathy features among youth are best understood as existing along a continuum. CONCLUSIONS: Although youth clearly vary in the degree to which they manifest psychopathy-like personality traits, there is no natural, discrete class of young \u27psychopaths.\u27 This finding has implications for developmental theory, treatment, assessment strategies, research, and clinical/forensic practice

In vivo generation of transplantable human hematopoietic cells from induced pluripotent stem cells

10.1182/blood-2012-06-434407Blood12181255-1264BLOO

Core-binding factor leukemia hijacks the T-cell–prone PU.1 antisense promoter

The blood system serves as a key model for cell differentiation and cancer. It is orchestrated by precise spatiotemporal expression of crucial transcription factors. One of the key master regulators in the hematopoietic systems is PU.1. Reduced levels of PU.1 are characteristic for human acute myeloid leukemia (AML) and are known to induce AML in mouse models. Here, we show that transcriptional downregulation of PU.1 is an active process involving an alternative promoter in intron 3 that is induced by RUNX transcription factors driving noncoding antisense transcription. Core-binding factor (CBF) fusions RUNX1-ETO and CBFβ-MYH11 in t(8;21) and inv(16) AML, respectively, activate the PU.1 antisense promoter that results in a shift from sense toward antisense transcription and myeloid differentiation blockade. In patients with CBF-AML, we found that an elevated antisense/sense transcript and promoter accessibility ratio represents a hallmark compared with normal karyotype AML or healthy CD34+ cells. Competitive interaction of an enhancer with the proximal or the antisense promoter forms a binary on/off switch for either myeloid or T-cell development. Leukemic CBF fusions thus use a physiological mechanism used by T cells to decrease sense transcription. Our study is the first example of a sense/antisense promoter competition as a crucial functional switch for gene expression perturbation by oncogenes. Hence, this disease mechanism reveals a previously unknown Achilles heel for future precise therapeutic targeting of oncogene-induced chromatin remodeling