Anhedonia in the psychosis risk syndrome: associations with social impairment and basal orbitofrontal cortical activity.

Background/objectives: Anhedonia is associated with poor social function in schizophrenia. Here, we examined this association in individuals at clinical high risk (CHR) for schizophrenia and related psychotic disorders, taking into account social anxiety. We then explored correlations between anhedonia and basal metabolic activity in selected forebrain regions implicated in reward processing.

Social inference in individuals at clinical high risk for psychosis.

Aim: Social cognition impairment is a hallmark of schizophrenia and contains multiple domains. The domain of social inference has been relatively understudied in schizophrenia and its risk states.

Methods: Social inference was assessed in 60 clinical high-risk (CHR) patients and 28 healthy control subjects, using the video social inference task.

Reasons for cannabis use among youths at ultra high risk for psychosis.

Aim: Cannabis use is prevalent in schizophrenia and its risk states, despite its association with anxiety and positive symptoms. While schizophrenia patients report using cannabis for mood enhancement and social motives, it is not known what motivates clinical high risk (CHR) patients to use cannabis.

Methods: Among 102 CHR patients, 24 (23%) endorsed cannabis use, and were queried as to reasons for use, using a scale previously administered in schizophrenia patients.

Spontaneous brain activity in combat related PTSD.

Posttraumatic stress disorder (PTSD) is a prevalent psychiatric disorder, especially in combat veterans. Existing functional neuroimaging studies have provided important insights into the neural mechanisms of PTSD using various experimental paradigms involving trauma recollection or other forms of emotion provocation. However it is not clear whether the abnormal brain activity is specific to the mental processes related to the experimental tasks or reflects general patterns across different brain states.

Prefrontal cortical inputs to the basal amygdala undergo pruning during late adolescence in the rat.

Transformations in affective and social behaviors, many of which involve amygdalar circuits, are hallmarks of adolescence in many mammalian species. In this study, using the rat as a model, we provide the first evidence that afferents of the basal amygdala (BA) undergo significant structural remodeling during adolescence. We used quantitative tract-tracing and gene expression profiling methods to characterize changes in the medial prefrontal cortical (mPFC) inputs to the BA across ages analogous to the late juvenile period [postnatal day (P) 25], late adolescence (P45), and adulthood (P90) in the rat.

The relationship of social function to depressive and negative symptoms in individuals at clinical high risk for psychosis.

Background: Social dysfunction is a hallmark symptom of schizophrenia which commonly precedes the onset of psychosis. It is unclear if social symptoms in clinical high-risk patients reflect depressive symptoms or are a manifestation of negative symptoms.

Method: We compared social function scores on the Social Adjustment Scale-Self Report between 56 young people (aged 13-27 years) at clinical high risk for psychosis and 22 healthy controls.

Temporal association of cannabis use with symptoms in individuals at clinical high risk for psychosis.

Background: Cannabis use is reported to increase the risk for psychosis, but no prospective study has longitudinally examined drug use and symptoms concurrently in clinical high risk cases.

Method: We prospectively followed for up to 2 years 32 cases who met research criteria for prodromal psychosis to examine the relationship between substance use and clinical measures.

Results: Cases with a baseline history of cannabis use (41%) were older, but did not differ in clinical measures.

Impact of ionizing radiation and genetic background on mammary tumorigenesis in p53-deficient mice.

Loss of p53 function is known to compromise cell cycle regulation, inductionof apoptosis, and DNA damage repair and can facilitate neoplastic transformation of cells. Mutations in the p53 gene are identified frequently in breast carcinomas. Li-Fraumeni patients inheriting a mutant p53 allele have an increased risk for developing tumors including breast cancer.

Growth retardation, DNA repair defects, and lack of spermatogenesis in BRCA1-deficient mice.

BRCA1 is a nuclear phosphoprotein expressed in a broad spectrum of tissues during cell division. The inheritance of a mutant BRCA1 allele dramatically increases a woman's lifetime risk for developing both breast and ovarian cancers. A number of mouse lines carrying mutations in the Brca1 gene have been generated, and mice homozygous for these mutations generally die before day 10 of embryonic development.

Effect of loss of P2Y(2) receptor gene expression on nucleotide regulation of murine epithelial Cl(-) transport.

Extracellular nucleotides are believed to be important regulators of ion transport in epithelial tissues as a result of their ability to activate cell surface receptors. Although numerous receptors that bind nucleotides have been identified, the complexity of this receptor family, combined with the lack of pharmacological agents specific for these receptors, has made the assignment of particular receptors and ligands to physiological responses difficult. Because ATP and UTP appear equipotent and equieffective in regulating ion transport in many epithelia, we tested the hypothesis that the P2Y(2) receptor (P2Y(2)-R) subtype mediates these responses in mouse epithelia, with gene targeting techniques.

Mammary tumor formation in p53- and BRCA1-deficient mice.

The inheritance of a mutant copy of the BRCA1 gene greatly increases a woman's lifetime risk for ovarian and breast cancer. While a homologous gene has been identified in mouse, mice carrying mutations in this gene do not display a detectable increase in tumor formation. To determine whether mutations in p53 might increase the incidence of tumors associated with the loss of BRCA1 function in mice, we have generated mice carrying mutations at both of these loci.

The relationship of chronic mucin secretion to airway disease in normal and CFTR-deficient mice.

In the cystic fibrosis (CF) patient, lung function decreases throughout life as a result of continuous cycles of infection, particularly with Pseudomonas aeruginosa and Staphylococcus aureus. The mechanism underlying the pathophysiology of the disease in humans has not been established. However, it has been suggested that abnormal, tenacious mucus, resulting perhaps from improper hydration from loss of Cl- secretion via the cystic fibrosis transmembrane conductance regulator (CFTR) protein, impairs clearance of bacteria from the CF airway and provides an environment favorable to bacterial growth.