Missed diagnosis of psychotic depression at 4 academic medical centers.

BACKGROUND: Major depressive disorder with psychotic features (psychotic depression), though occurring relatively frequently in the general population, is a commonly missed psychiatric diagnosis. OBJECTIVE: To ascertain accuracy of diagnosis of psychotic depression among inpatients at 4 academic medical centers and explore whether presenting symptoms, treatment setting, and physician's level of training affect the accuracy of diagnosis. METHOD: The medical records of 65 patients who met DSM-IV criteria for psychotic depression following systematic assessment were analyzed to ascertain the concordance between chart diagnoses and research diagnoses arrived at using the Structured Clinical Interview for DSM-IV. The patients were participants in the National Institute of Mental Health Study of Pharmacotherapy of Psychotic Depression, conducted from December 28, 2002, through June 18, 2004, at 4 academic medical centers. For each patient's hospital visit, separate standardized data forms were completed on the basis of each physician's assessment of the patient prior to screening for the study. Hospital records from the emergency room and from admission to psychiatric units were reviewed. Among these 65 patients, 130 chart diagnoses had been made. RESULTS: Psychotic depression had not been diagnosed prior to research assessments for 27% of the 130 diagnoses in our sample. The 3 most common diagnoses assigned to patients meeting research criteria for psychotic depression were major depressive disorder without psychotic features, depression not otherwise specified, and mood disorder not otherwise specified. Failure to identify psychotic depression was more likely when symptoms of depressed mood, hallucinations, or delusions were not noted in the medical record (all p < .005). The accuracy of diagnoses was greater on inpatient units than in emergency rooms (chi(2) = 7.64, p < .01). CONCLUSION: The diagnosis of psychotic depression is frequently missed in emergency room and inpatient settings. The findings of this study are sobering given the serious morbidity and mortality of psychotic depression and the implications for treatment if an inaccurate diagnosis is made. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00056472.

Impact on health care workers employed in high-risk areas during the Toronto SARS outbreak.

BACKGROUND: A number of publications focusing on health care workers (HCWs) during a severe acute respiratory syndrome (SARS) outbreak have suggested that HCWs experienced psychological distress, particularly increased levels of posttraumatic stress symptomatology (PTSS). Factors contributing to increased distress in HCWs working in high-risk areas treating patients with SARS have not been fully elucidated. The goal of this study was to quantify the psychological effects of working in a high-risk unit during the SARS outbreak. METHODS: HCWs in a Toronto hospital who worked in high-risk areas completed a questionnaire regarding their attitude toward the SARS crisis along with the Impact of Event Scale-Revised, which screens for PTSS. The comparison group consisted of clinical units that had no contact with patients infected with SARS. RESULTS: Factors that were identified to cause distress in the 248 respondent HCWs were the following: (a) perception of risk to themselves, (b) impact of the SARS crisis on their work life, (c) depressive affect, and (d) working in a high-risk unit. In addition, HCWs who cared for only one SARS patient in comparison to those caring for multiple SARS patients experienced more PTSS. CONCLUSIONS: As expected, HCWs who were working in high-risk units experienced greater distress. Contrary to expectations, HCWs who experienced greater contact with SARS patients while working in the high-risk units were less distressed. This suggests that HCW experience in treating patients infected with SARS may be a mediating factor that could be amenable to intervention in future outbreaks.

Molecular and biochemical mechanisms in teratogenesis involving reactive oxygen species.

Developmental pathologies may result from endogenous or xenobiotic-enhanced formation of reactive oxygen species (ROS), which oxidatively damage cellular macromolecules and/or alter signal transduction. This minireview focuses upon several model drugs (phenytoin, thalidomide, methamphetamine), environmental chemicals (benzo[a]pyrene) and gamma irradiation to examine this hypothesis in vivo and in embryo culture using mouse, rat and rabbit models. Embryonic prostaglandin H synthases (PHSs) and lipoxygenases bioactivate xenobiotics to free radical intermediates that initiate ROS formation, resulting in oxidation of proteins, lipids and DNA. Oxidative DNA damage and embryopathies are reduced in PHS knockout mice, and in mice treated with PHS inhibitors, antioxidative enzymes, antioxidants and free radical trapping agents. Thalidomide causes embryonic DNA oxidation in susceptible (rabbit) but not resistant (mouse) species. Embryopathies are increased in mutant mice deficient in the antioxidative enzyme glucose-6-phosphate dehydrogenase (G6PD), or by glutathione (GSH) depletion, or inhibition of GSH peroxidase or GSH reductase. Inducible nitric oxide synthase knockout mice are partially protected. Inhibition of Ras or NF-kB pathways reduces embryopathies, implicating ROS-mediated signal transduction. Atm and p53 knockout mice deficient in DNA damage response/repair are more susceptible to xenobiotic or radiation embryopathies, suggesting a teratological role for DNA damage, consistent with enhanced susceptibility to methamphetamine in ogg1 knockout mice with deficient repair of oxidative DNA damage. Even endogenous embryonic oxidative stress carries a risk, since untreated G6PD- or ATM-deficient mice have increased embryopathies. Thus, embryonic processes regulating the balance of ROS formation, oxidative DNA damage and repair, and ROS-mediated signal transduction may be important determinants of teratological risk.

The peroxynitrite pathway in development: phenytoin and benzo[a]pyrene embryopathies in inducible nitric oxide synthase knockout mice.

Nitric oxide generated by nitric oxide synthases (NOSs) can react with reactive oxygen species (ROS), forming peroxynitrite, which may contribute to the ROS-initiated macromolecular damage implicated in the embryopathic effects of both endogenous and drug-enhanced oxidative stress. Inducible NOS (iNOS) is nonconstitutive in most tissues, and its embryonic expression and developmental importance are unknown. Herein, during organogenesis (Gestational Days 9 and 10), wild-type B6129PF2 embryos in culture were highly susceptible to the ROS-initiating teratogens phenytoin and benzo[a]pyrene, whereas iNOS knockout embryos were substantially but not completely protected (p < .05), implicating iNOS in the embryopathic mechanism. However, in contrast to prostaglandin H synthase-catalyzed teratogen bioactivation and ROS formation, which occurs within the embryo, in vivo iNOS expression was limited to placental tissue. These results suggest that the diffusion of nitric oxide from placental progenitor tissue (ectoplacental cone) to embryonic target tissues contributes to the embryopathic effects of ROS-initiating teratogens in embryo culture, which may constitute a mechanism by which embryonic determinants of ROS-mediated teratogenesis can be modulated by maternal extra-embryonic processes.