Myeloid expression of the AP-1 transcription factor JUNB modulates outcomes of type 1 and type 2 parasitic infections.

Activation of macrophages is a key step in the initiation of immune responses, but the transcriptional mechanisms governing macrophage activation during infection are not fully understood. It was recently shown that the AP-1 family transcription factor JUNB positively regulates macrophage activation in response to Toll-like receptor agonists that promote classical or M1 polarization, as well as to the cytokine interleukin-4 (IL-4), which elicits an alternatively activated or M2 phenotype. However, a role for JUNB in macrophage activation has never been demonstrated in vivo. Here, to dissect the role of JUNB in macrophage activation in a physiological setting, mice lacking JUNB specifically in myeloid cells were tested in two infection models: experimental cerebral malaria, which elicits a pathological type 1 immune response, and helminth infection, in which type 2 responses are protective. Myeloid-restricted deletion of Junb reduced type 1 immune activation, which was associated with reduced cerebral pathology and improved survival during infection with Plasmodium berghei. Myeloid JUNB deficiency also compromised type 2 activation during infection with the hookworm Nippostrongylus brasiliensis, leading to diminished cytokine production and eosinophil recruitment and increased parasite burden. These results demonstrate that JUNB in myeloid cells shapes host responses and outcomes during type 1 and type 2 infections.

EEG in adults in the laboratory or at the patient's bedside.

Electroencephalogram (EEG) recording in the laboratory lasts at least 20 minutes and uses 19 active electrodes. It includes rest periods, stimulation procedures, a 3-mn hyperventilation period and intermittent photic stimulation (IPS). Recorded at the bedside, the EEG uses at least eight electrodes; the stimulation procedures, duration of the EEG and need to repeat the examination depend on the indication. Simultaneous video recording is recommended. The EEG report describes the basic rhythm, its reactivity and pathological activities, whether epileptic or not, and their organization. The synthetic conclusion interprets the results while taking into account the clinical context and contributes, if possible, diagnostic and/or therapeutic help in patient management. EEG performed as soon as possible after a seizure is essential for the diagnosis and initial management of epilepsy. It is helpful to characterize the epileptic syndrome in order to initiate optimal treatment. EEG is also useful in managing the withdrawal of antiepileptic drugs. EEG is also extremely useful in case of impaired consciousness, confusional state or even acute or subacute cognitive disorders. It is the only available tool able to validate the diagnosis of non-convulsive status epilepticus presenting with confusional state. EEG helps in the diagnosis of toxic or metabolic encephalopathy and can assess its severity, especially in hepatic encephalopathy. Except in rare exceptions, EEG is not routinely indicated for the evaluation of typical vasovagal syncope, headaches, dizziness, typical transient global amnesia and transient ischemic attack. EEG is irreplaceable in the diagnosis and management of certain severe and frequent pathologies involving the cerebral cortex.

[French guidelines on electroencephalogram]. / Recommandations françaises sur l'électroencéphalogramme.

Electroencephalography allows the functional analysis of electrical brain cortical activity and is the gold standard for analyzing electrophysiological processes involved in epilepsy but also in several other dysfunctions of the central nervous system. Morphological imaging yields complementary data, yet it cannot replace the essential functional analysis tool that is EEG. Furthermore, EEG has the great advantage of being non-invasive, easy to perform and allows control tests when follow-up is necessary, even at the patient's bedside. Faced with the advances in knowledge, techniques and indications, the Société de Neurophysiologie Clinique de Langue Française (SNCLF) and the Ligue Française Contre l'Épilepsie (LFCE) found it necessary to provide an update on EEG recommendations. This article will review the methodology applied to this work, refine the various topics detailed in the following chapters. It will go over the summary of recommendations for each of these chapters and underline proposals for writing an EEG report. Some questions could not be answered by the review of the literature; in those cases, an expert advice was given by the working and reading groups in addition to the guidelines.

Developing effective treatments for posttraumatic disorders among people with severe mental illness.

OBJECTIVE: The purpose of the study was to examine strategies for developing effective interventions for clients who have both serious mental illness and posttraumatic symptoms. METHODS: The authors conducted searches for articles published between 1970 and 2000, using MEDLINE, PsycLIT, and PILOTS. They assessed current practices, interviewed consumers and providers, and examined published and unpublished documents from consumer groups and state mental health authorities. RESULTS AND CONCLUSIONS: Exposure to trauma, particularly violent victimization, is endemic among clients with severe mental illness. Multiple psychiatric and behavioral problems are associated with trauma, but posttraumatic stress disorder (PTSD) is the most common and best-defined consequence of trauma. Mental health consumers and providers have expressed concerns about several trauma-related issues, including possible underdiagnosis of PTSD, misdiagnosis of other psychiatric disorders among trauma survivors, incidents of retraumatization in the mental health treatment system, and inadequate treatment for trauma-related disorders. Despite consensus that trauma and PTSD symptoms should be routinely evaluated, valid assessment techniques are not generally used by mental health care providers. PTSD is often untreated among clients with serious mental illness, or it is treated with untested interventions. It is important that policy makers, service system administrators, and providers recognize the prevalence and impact of trauma in the lives of people with severe mental illness. The development of effective treatments for this population requires a rational, orderly process, beginning with the testing of theoretically grounded interventions in controlled clinical trials.

Determinants of risk behavior for human immunodeficiency virus/acquired immunodeficiency syndrome in people with severe mental illness.

We examined the prevalence and correlates of human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) risk behaviors in a large sample of severely mentally ill (SMI) patients. Risk levels were correlated with demographic factors, diagnosis, symptom severity, trauma history, post-traumatic stress disorder (PTSD), substance use disorder (SUD), and sexual orientation. SMI clients from urban and rural settings (N = 275) were assessed regarding HIV/AIDS risk behaviors, and hypothesized risk factors. Patients exhibited substantial levels of risky behavior, particularly sexual risk. Correlates of increased risk included SUD, trauma, male homosexual orientation, younger age, and symptom severity. Structural equation modeling identified SUD and sexual orientation as the primary determinants of both drug and sexual risk behavior. We conclude that specific illness related variables appear to have less impact on risk behavior among people with SMI than previously hypothesized. Substance abuse prevention and treatment may be the most effective means of reducing HIV risk in this population.

Psychometric evaluation of trauma and posttraumatic stress disorder assessments in persons with severe mental illness.

Interrater reliability, internal consistency, test-retest reliability, and convergent validity were examined for the Trauma History Questionnaire (THQ), the Clinician-Administered Posttraumatic Stress Disorder (PTSD) Scale (CAPS), and the PTSD Checklist (PCL) in 30 clients with severe mental illnesses. Interrater reliability for the THQ and CAPS was high, as was internal consistency of CAPS and PCL subscales. The test-retest reliability of the THQ was moderate to high for different traumas. PTSD diagnoses on the CAPS and PCL showed moderate test-retest reliability. Lower levels of test-retest reliability for PTSD diagnoses were related to psychosis diagnoses and symptoms. However, when more stringent criteria for PTSD were used on the CAPS, it had excellent test-retest reliability across all clients. CAPS and PCL diagnoses of PTSD showed moderate convergent validity. The results support the reliability of trauma and PTSD assessments in clients with severe mental illness.

Prevalence of HIV, hepatitis B, and hepatitis C in people with severe mental illness.

OBJECTIVES: This study assessed seroprevalence rates of HIV, hepatitis B virus (HBV), and hepatitis C virus (HCV) among individuals with severe mental illness. METHODS: Participants (n = 931) were patients undergoing inpatient or outpatient treatment in Connecticut, Maryland, New Hampshire, or North Carolina. RESULTS: The prevalence of HIV infection in this sample (3.1%) was approximately 8 times the estimated US population rate but lower than rates reported in previous studies of people with severe mental illness. Prevalence rates of HBV (23.4%) and HCV (19.6%) were approximately 5 and 11 times the overall estimated population rates for these infections, respectively. CONCLUSIONS: Elevated rates of HIV, HBV, and HCV were found. Of particular concern are the high rates of HCV infection, which are frequently undetected. Individuals with HCV infection commonly fail to receive appropriate treatment to limit liver damage and unknowingly may be a source of infection to others.

Recent victimization in women and men with severe mental illness: prevalence and correlates.

The problem of violence against individuals with severe mental illness (SMI) has received relatively, little notice, despite several studies suggesting an exceptionally high prevalence of victimization in this population. This paper describes the results of an investigation of the prevalence and correlates of past year physical and sexual assault among a large sample of women and men with SMI drawn from inpatient and outpatient settings across 4 states. Results confirmed preliminary findings of a high prevalence of victimization in this population (with sexual abuse more prevalent for women and physical abuse more prevalent for men), and indicated the existence of a range of correlates of recent victimization, including demographic factors and living circumstances, history of childhood abuse, and psychiatric illness severity and substance abuse. The research and clinical implications of these findings are discussed.

HIV-related services for persons with severe mental illness: policy and practice in New Hampshire community mental health.

Rates of HIV and HIV risk behaviors are elevated among people with severe mental illnesses (SMI). Little is known about the extent to which community mental health (CMH) centers screen, refer, and educate their clients regarding HIV and sexually transmitted diseases (STDs). The authors surveyed CMH administrators and clinicians in New Hampshire regarding HIV/STD policy, practices, knowledge, and attitudes. HIV/STD service availability varied, and the amount of services provided was unrelated to the prevalence of HIV and AIDS in that region. Clinicians were knowledgeable about general HIV information but lacked specific knowledge about HIV related to persons with SMI. CMH staff had positive attitudes about helping clients with HIV issues. Administrators were interested in receiving training. Policy leadership, CMH practice guidelines, and training are warranted in light of the pressing public health implications of HIV/STDs among people with SMI.

A comparative study of trauma and posttraumatic stress disorder prevalence in epilepsy patients and psychogenic nonepileptic seizure patients.

PURPOSE: This study tests the hypothesis that trauma histories, including histories of physical and sexual abuse, and posttraumatic stress disorder (PTSD) are more prevalent in psychogenic non-epileptic seizure (NES) patients than in epilepsy patients. METHODS: Thirty-five inpatients with intractable seizures were evaluated for trauma history and PTSD. After these assessments, patients were diagnosed as having either epileptic or nonepileptic seizures through EEG monitoring. RESULTS: NES diagnosis correlated with PTSD and total number of lifetime traumas, adult traumas, and abuse traumas. Contrary to previous hypotheses, reported childhood sexual abuse (CSA) did not correlate significantly with NES diagnosis. However, CSA predicted PTSD in a discriminant analysis. CONCLUSIONS: We found evidence for the hypothesized relations between trauma, abuse, PTSD, and NES diagnosis. However, elevated levels in both seizure-disorder groups suggest that routine assessment for abuse, trauma, and PTSD might facilitate medical care and treatment for all intractable seizure patients.

Prosody and lexical accuracy in flat affect schizophrenia.

To test the hypothesis that flat affect in schizophrenia involves a motor-expressive deficiency, but not an emotional deficiency, we compared the acoustic properties of speech that are used to express emotion with the emotional content of the words. DSM-III-R schizophrenic patients were divided into flat (N=20) and non-flat affect (N=26) groups on the basis of rating-scale scores. Twenty normal subjects also were included. Subjects were recorded on audio tape as they described a happy and a sad experience for about 10 min. The recordings were analyzed acoustically for fluency and for two types of prosody: inflection and emphasis. Words from transcriptions of the recordings were sorted by content analysis software into psychologically meaningful categories; we compared 'pleasure' and 'distress' word categories. Patients with flat affect spoke with less inflection, and were less fluent. However, they were similar to the other groups in the rate at which they used 'pleasure' words to describe happy experiences and 'distress' words to describe sad experiences. The behavioral deficiency in flat affect appears to be restricted to reduced activity in communicative motor channels. Other aspects of emotion processing seem intact.

The relationship between trauma, PTSD, and medical utilization in three high risk medical populations.

OBJECTIVE: Increased use of medical and psychiatric services has been reported as a correlate of exposure to trauma. Recent studies suggest that: 1) physical and sexual abuse traumas are particularly associated with increased utilization and 2) posttraumatic stress disorder (PTSD), a common sequela of abuse, mediates the relationship between trauma exposure andelevated utilization. The goal of this study was to explore the relationships between trauma, abuse, PTSD, and medical utilization in three medical help seeking groups reported to be at high risk for trauma exposure. METHOD: One hundred and seven patients receiving care at a university-affiliated medical center were surveyed for trauma history and PTSD using the Trauma History Questionnaire (THQ) and the PTSD Checklist (PCL). The sample included: forty-eight gynecologic outpatients, thirty-five inpatients with seizure disorders, and twenty-four psychiatric inpatients with non-PTSD admitting diagnoses. Medical utilization data were obtained from a computerized medical center data base. RESULTS: Ninety-six patients reported a trauma history. Of these patients, sixty-six reported abuse and forty-five qualified for PTSD diagnoses. Total number of traumas and reported sexual and physical abuse correlated significantly with elevated medical utilization and PTSD prevalence. PTSD diagnosis was not significantly correlated with utilization, but the five highest utilizers received PTSD diagnoses. CONCLUSIONS: Study results supported hypotheses regarding the relation of trauma exposure to medical utilization, but were less clear about the mediating role of PTSD. These findings suggest that routine screening of high-risk patient groups might promote timely identification of trauma history and PTSD, and subsequently impact health care utilization.

Substance use disorder in hospitalized severely mentally ill psychiatric patients: prevalence, correlates, and subgroups.

The prevalence and demographic and clinical correlates of lifetime substance use disorders were examined in a cohort of 325 recently hospitalized psychiatric patients (53% schizophrenia or schizoaffective disorder). Alcohol use was the most common type of substance use disorder, followed by cannabis and cocaine use. Univariate analyses indicated that gender (male), age (younger), education (less), history of time in jail, conduct disorder symptoms, and antisocial personality disorder symptoms were predictive of substance use disorders. Lifetime cannabis use disorder was uniquely predicted by marital status (never married) and fewer psychiatric hospitalizations during the previous 6 months. Optimal classification tree analysis, an exploratory, nonlinear method of identifying patient subgroups, was successful in predicting 74 percent to 86 percent of the alcohol, cannabis, and cocaine use disorders. The implications of this method for identifying specific patient subgroups and service needs are discussed.

HIV risk factors among people with severe mental illness in urban and rural areas.

No studies have reported HIV risk behavior in rural populations with severe mental illness. A total of 84 rural patients with severe mental illness in New Hampshire and 158 urban patients in Baltimore were interviewed about their HIV risk behavior in the past six months using the Risk Assessment Battery, a 38-item structured clinical interview. Rates of sexual and drug risk behavior among rural patients were significantly lower than among urban patients. Regression analyses showed that urban setting, younger age, never having been married, and a bisexual or gay orientation significantly predicted higher HIV risk scores. The differences in risk behaviors may reflect urban-rural differences in drug availability and sexual practices.

Conduct disorder, antisocial personality disorder and substance use disorders in schizophrenia and major affective disorders.

OBJECTIVE: To examine the relationships between childhood conduct disorder (CD), antisocial personality disorder (ASPD) and substance use disorders (substance abuse or substance dependence) in psychiatric patients with severe mental illness. METHOD: Substance use-related problems on screening instruments, lifetime and recent prevalence of substance use disorders, and family history of substance use disorder were evaluated in four groups of 293 patients with mainly schizophrenia-spectrum and major affective disorders: No ASPD/CD, CD Only, Adult ASPD Only, Full ASPD. RESULTS: Full ASPD was strongly related to all measures of substance use problems and disorders, as well as fathers' history of substance use disorder. The odds ratios for Full ASPD and substance use disorders ranged between 3.96 (lifetime cannabis use disorder) to 11.35 (recent cocaine use disorder). To a lesser extent, patients with CD Only or Adult ASPD Only were also at increased risk for having substance use disorders compared to the No ASPD/CD patients. CONCLUSIONS: Childhood CD and adult ASPD represent significant risk factors for substance use disorders in patients with schizophrenia-spectrum and major affective disorders. Considering other research indicating that CD and ASPD have a higher prevalence in patients with severe mental illness, the present findings suggest that CD and ASPD could reflect a common factor that independently increases patients' vulnerability to both psychiatric and substance use disorders.

Reliability of reports of violent victimization and posttraumatic stress disorder among men and women with serious mental illness.

Although violent victimization is highly prevalent among men and women with serious mental illness (SMI; e.g., schizophrenia, bipolar disorder), future research in this area may be impeded by controversy concerning the ability of individuals with SMI to report traumatic events reliably. This article presents the results of a study exploring the temporal consistency of reports of childhood sexual abuse, adult sexual abuse, and adult physical abuse, as well as current symptoms of posttraumatic stress disorder (PTSD) among 50 people with SMI. Results show that trauma history and PTSD assessments can, for the most part, yield reliable information essential to further research in this area. The study also demonstrates the importance of using a variety of statistical methods to assess the reliability of self-reports of trauma history.

Trauma and posttraumatic stress disorder in severe mental illness.

This research assessed the lifetime prevalence of traumatic events and current posttraumatic stress disorder (PTSD) in 275 patients with severe mental illness (e.g., schizophrenia and bipolar disorder) receiving public mental health services in Concord and Manchester, New Hampshire, and Baltimore, Maryland. Lifetime exposure to traumatic events was high, with 98% of the sample reporting exposure to at least 1 traumatic event. The rate of PTSD in our sample was 43%, but only 3 of 119 patients with PTSD (2%) had this diagnosis in their charts. PTSD was predicted most strongly by the number of different types of trauma, followed by childhood sexual abuse. The findings suggest that PTSD is a common comorbid disorder in severe mental illness that is frequently overlooked in mental health settings.

Dartmouth Assessment of Lifestyle Instrument (DALI): a substance use disorder screen for people with severe mental illness.

OBJECTIVE: Despite high rates of co-occurring substance use disorder in people with severe mental illness, substance use disorder is often undetected in acute-care psychiatric settings. Because underdetection is related to the failure of traditional screening instruments with this population, the authors developed a new screen for detection of substance use disorder in people with severe mental illness. METHOD: On the basis of criterion ("gold standard") diagnoses of substance use disorder for 247 patients admitted to a state hospital, the authors used logistic regression to select the best items from 10 current screening instruments and constructed a new instrument. They then tested the validity of the new instrument, compared with other screens, on an independent group of 73 admitted patients. RESULTS: The new screening instrument, the Dartmouth Assessment of Lifestyle Instrument (DALI), is brief, is easy to use, and exhibits high classification accuracy for both alcohol and drug (cannabis and cocaine) use disorders. Receiver operating characteristic curves showed that the DALI functioned significantly better than traditional instruments for both alcohol and drug use disorders. CONCLUSIONS: Initial findings suggest the DALI may be useful for detecting substance use disorder in acutely ill psychiatric patients. Further research is needed to validate the DALI in other settings and with other groups of psychiatric patients.

Physical and sexual assault history in women with serious mental illness: prevalence, correlates, treatment, and future research directions.

An emerging body of research on the physical and sexual abuse of seriously mentally ill (SMI) women documents a high incidence and prevalence of victimization within this population. While causal links are not well understood, there is convergent evidence that victimization of SMI women is associated with increased symptom levels, HIV-related risk behaviors, and such comorbid conditions as homelessness and substance abuse. These abuse correlates may influence chronicity, service utilization patterns, and treatment alliance. This article reviews the research literature on the prevalence, symptomatic and behavioral correlates, and treatment of abuse among SMI women, particularly women with schizophrenia. Within each topic, we discuss relevant research findings, limitations of available studies, and key questions that remain unanswered. We also discuss mechanisms that may underlie the relationship between trauma and schizophrenia-spectrum disorders. We conclude by outlining directions for future research in this area.

New directions for treatment research on sequelae of sexual abuse in persons with severe mental illness.

Sexual abuse in childhood is increasingly recognized as an important etiologic component in a number of psychiatric disorders. One-quarter to one-third of all female children suffer sexual abuse before their eighteenth birthday, and at least one half of women with severe mental illness acknowledge such events. An even higher percentage of a particularly vulnerable group, dually diagnosed homeless women, appear to have a premorbid history of childhood victimization. In this paper, we review the emergent literature on childhood abuse, its sequelae and treatment; and discuss the implications of these data for the development of new approaches to trauma recovery in people with severe mental illness.