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.

Verbal behavior and schizophrenia. The semantic dimension.

Through the use of computer analysis, the content of the speech of schizophrenics is shown to be distinct from that of the speech of nonschizophrenic psychiatric patients. The data shed light on qualities that delineate some aspects of "bizarreness" in speech of schizophrenics, provide some insight into the diversity of postulated "defects" in schizophrenic thinking, and provide further understanding of the diagnostic process in schizophrenia.

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.

Computer content analysis of schizophrenic speech: a preliminary report.

Computer analysis significantly differtiated the thermatic content of the free speech of 10 schizophrenic patients from that of 10 nonschizophrenic patients and from the content of transcripts of dream material from 10 normal subjects. Schizophrenic patients used the thematic categories in factor 1 (the "schizophrenic factor") 3 times more frequently than the nonschizophrenics and 10 times more frequently than the normal subjects (p smaller than 01). In general, the language content of the schizophrenic patient mirrored an almost agitated attempt to locate oneself in time and space and to defend against internal discomfort and confusion. The authors discuss the implications of this study for future research.

Premilitary MMPI scores as predictors of combat-related PTSD symptoms.

OBJECTIVE: The authors used data collected before military service to assess predictors of combat-related lifetime symptoms of posttraumatic stress disorder (PTSD). METHOD: The subjects were 131 male Vietnam and Vietnam-era veterans who had taken the MMPI in college and who were interviewed as adults with the Structured Clinical Interview for DSM-III-R. Scores on the basic MMPI scales were used to predict combat exposure, lifetime history of any PTSD symptoms given exposure, and lifetime PTSD classification (symptoms only, subthreshold PTSD, or full PTSD). RESULTS: Group means on the MMPI scales were within the normal range. No scale predicted combat exposure. Hypochondriasis, psychopathic deviate, masculinity-femininity, and paranoia scales predicted PTSD symptoms. Depression, hypomania, and social introversion predicted diagnostic classification among subjects with PTSD symptoms. The effects persisted when amount of combat exposure was controlled for. CONCLUSIONS: Pre-military personality can affect vulnerability to lifetime PTSD symptoms in men exposed to combat.

The language of paranoia.

In order to assess which of three current models is most useful in understanding paranoia, the authors applied computer speech content analysis to 55 patients--24 of whom were in four groups expressing paranoid delusions and 31 of whom were in four groups not expressing such delusions. The results delineated a semantic or verbal profile of paranoid self-presentation. This self-presentation is more identifiable than the effects of any other patient characteristic, even if the delusion is not discussed by the patient. The strength of the statistical evidence supports the model of paranoid delusions as a separate disease rather than as a subtype of schizophrenia or as a trait that exists on a spectrum from normality to pathology.

Diagnosis and pharmacotherapy issues in the care of Hispanics in the public sector.

Clinical data from 1,752 ambulatory patients treated at five public mental health clinics were used to test hypotheses concerning the diagnoses and psychopharmacotherapy of Hispanic patients compared with Anglos and blacks. Hispanics were less likely than the other two groups to be labeled schizophrenic but more likely to be diagnosed as having other mental illnesses. Hispanics were less likely to receive medication than the other two groups. However, when pharmacotherapy was used there were no significant differences among groups in the number of medications prescribed. There were no differences among the groups in the doses prescribed.

Linguistic dimensions of affect and thought in somatization disorder.

DSM-III has established diagnostic criteria that separate somatization disorder from other overlapping symptom configurations. Nevertheless, information regarding the experience of somatization disorder is far from complete. Terms such as "masked depression" or "alexithymia" imply that a disturbance of affect is a central but guarded issue for at least some somatizing patients. Through content analysis of speech, the authors investigated the self-experience of somatization disorder in relation to affective disorder. Rather than defended depression, a distinctive characteristic found in the language of patients with somatization disorder reflects a confused, negative self-identity.

Diagnostic classification through content analysis of patients' speech.

Speech samples from 71 patients in four diagnostic groups were analyzed by two quantitative methods of speech content analysis, the results of which were entered into a discriminant analysis to test whether patients could be accurately classified back into their appropriate diagnostic groups. These classifications were compared with classifications made by two psychiatrists, blind to the patients' diagnoses, who read transcripts of the speech samples. The results suggest that data from the systematic quantification of lexical choice can be used to classify patients into their respective diagnostic groups and that this classification compares favorably with that done by psychiatric raters.

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.

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.

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.

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.

Change in MMPI scores from college to adulthood as a function of military service.

We examined changes in Minnesota Multiphasic Personality Inventory scores from adolescence to adulthood in a longitudinal study of 540 men who attended college during the Vietnam War. Using change scores that were adjusted for initial values, we compared civilians to veterans who were grouped according to combat exposure: none, peripheral, or direct. In cross-sectional analyses, the groups differed only as adults. Groups were similar in relative stability but differed by multivariate analysis in absolute change on the clinical scales. Only veterans with peripheral exposure differed from civilians in multivariate contrasts, even after controlling for premilitary variables. Effect sizes were small. Results suggest that combat exposure does not produce uniformly negative outcomes and may have positive effects in select populations.

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.

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.

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.

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.

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.