Proinflammatory and "resiliency" proteins in the CSF of patients with major depression.

BACKGROUND: A number of studies have shown that elevated levels of inflammatory cytokines may promote depression and suicidal ideation and that neuroprotective peptides may decrease the response to stress and depression. In this study, cerebrospinal fluid (CSF) levels of three inflammatory cytokines (IL-1, IL-6, and tumor necrosis factor α (TNFα)) and two putative "resiliency" neuropeptides (brain-derived neurotrophic factor (BDNF) and neuropeptide Y (NPY)) were compared between patients with depression and healthy controls. METHODS: Eighteen patients with major depression and 25 healthy controls underwent a lumbar puncture; CSF samples were withdrawn and assayed for IL-1, IL-6, TNFα, BDNF, and NPY levels. Patients with depression were then entered into an 8-week treatment protocol and had repeated lumbar puncture procedures post-treatment. RESULTS: Contrary to prediction, we found that at baseline depressed patients had higher CSF NPY concentration compared to the normal comparison group. Within the depressed patients, we found several statistically significant correlations between elevated CSF cytokine levels and clinical severity. CONCLUSION: Despite the small sample size, given the challenges in obtaining CSF from patients with depression these data are of interest in confirming some aspects of the inflammatory hypothesis of depression.

Site matters: winning the hearts and minds of patients in a cardiology clinic.

BACKGROUND: In medical care settings, mental health symptoms of depression and distress are associated with poor medical outcomes, yet they are often underrecognized. OBJECTIVE: Authors sought to examine the effect of having immediate mental-health screening in the cardiology clinic. METHOD: The Patient Health Questionnaire and the Impact of Event Scale were used to screen for depression and distress in 316 patients at an urban cardiology clinic. Because of poor follow-up rates, a psychiatrist was placed on the premises of the cardiology clinic to facilitate referrals. RESULTS: Placing a psychiatrist within the cardiology clinic significantly improved the rate of successful referrals. CONCLUSION: Because 45 patients (14%) endorsed suicidal thoughts, authors conclude that mental health screening programs should include an immediate evaluation by a clinician.

Childhood abuse, nonadherence, and medical outcome in pediatric liver transplant recipients.

OBJECTIVE: The study assessed the relationship between a history of child abuse, nonadherence to medications, and medical outcome in children who had a liver transplant. METHOD: Abuse history for children and adolescents ages 8 to 21 who underwent a liver transplantation at Mount Sinai Medical Center in New York was obtained in interviews in 2002. Adherence to tacrolimus was assessed from January 1 to December 31, 2003 by computing the SD of a series of medication blood levels for each patient. Biopsy-proven rejection episodes, degree of fluctuation of alanine aminotransferase (ALT), and maximal ALT levels were recorded as indicators of medical outcome. RESULTS: Of 72 eligible patients, 56 were evaluated. Five had documented abuse. Abused children were less adherent to their medication regimen (p = .02; 95% confidence interval [CI] -2.66 to -0.24), had poor disease control (higher maximal ALT, p <.01; 95% CI -613.72 to -249.55), had greater fluctuation in ALT levels (p <.01; 95% CI -151.19 to -65.91), and suffered more biopsy-proven rejection episodes (two episodes in the abused cohort versus none in the rest) in 2003. CONCLUSIONS: A history of child abuse is a significant risk factor for poor outcome posttransplantation and should be evaluated routinely. Adherence to medications can be a target for intervention in patients with a history of abuse.

Mood disorders in the medically ill: scientific review and recommendations.

OBJECTIVE: The purpose of this review is to assess the relationship between mood disorders and development, course, and associated morbidity and mortality of selected medical illnesses, review evidence for treatment, and determine needs in clinical practice and research. DATA SOURCES: Data were culled from the 2002 Depression and Bipolar Support Alliance Conference proceedings and a literature review addressing prevalence, risk factors, diagnosis, and treatment. This review also considered the experience of primary and specialty care providers, policy analysts, and patient advocates. The review and recommendations reflect the expert opinion of the authors. STUDY SELECTION/DATA EXTRACTION: Reviews of epidemiology and mechanistic studies were included, as were open-label and randomized, controlled trials on treatment of depression in patients with medical comorbidities. Data on study design, population, and results were extracted for review of evidence that includes tables of prevalence and pharmacological treatment. The effect of depression and bipolar disorder on selected medical comorbidities was assessed, and recommendations for practice, research, and policy were developed. CONCLUSIONS: A growing body of evidence suggests that biological mechanisms underlie a bidirectional link between mood disorders and many medical illnesses. In addition, there is evidence to suggest that mood disorders affect the course of medical illnesses. Further prospective studies are warranted.

Elevated maternal interleukin-8 levels and risk of schizophrenia in adult offspring.

OBJECTIVE: Many studies have implicated prenatal infection in the etiology of schizophrenia. Cytokines, a family of soluble polypeptides, are critically important in the immune response to infection and in other inflammatory processes. The goal of this study was to determine whether second-trimester levels of four cytokines-interleukin-8 (IL-8), interleukin-1beta (IL-1beta), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-alpha)-are higher in the mothers of offspring who later developed schizophrenia spectrum disorders than in matched comparison subjects. METHOD: The authors conducted a nested case-control study of maternal serum cytokine levels in a large birth cohort, born 1959-1967. Cases (N=59) were subjects diagnosed with schizophrenia spectrum disorders (mostly schizophrenia and schizoaffective disorder) who had available second-trimester maternal serum samples. Comparison subjects (N=105) were members of the birth cohort, had not been diagnosed with a schizophrenia spectrum disorder or major affective disorder, and were matched to subjects with schizophrenia for date of birth, gender, length of time in the cohort, and availability of maternal sera. Maternal second-trimester serum levels of IL-8, IL-1beta, IL-6, and TNF-alpha were determined by sandwich enzyme-linked immunosorbent assay. RESULTS: The second-trimester IL-8 levels in mothers of offspring with schizophrenia spectrum disorders were significantly higher than those of the mothers of comparison subjects. There were no differences between subjects with schizophrenia and comparison subjects with respect to maternal levels of IL-1beta, IL-6, or TNF-alpha. CONCLUSIONS: Using prospectively collected prenatal sera in a large and well-characterized birth cohort, the authors have documented a significant association between maternal IL-8 level during the second trimester and risk of schizophrenia spectrum disorders in the offspring. These findings provide further support for a substantive role of in utero infection or inflammation in the etiology of schizophrenia. Moreover, these results may have important implications for elucidating the mechanisms by which disrupted fetal development raises the risk of this disorder.

Rodent doxapram model of panic: behavioral effects and c-Fos immunoreactivity in the amygdala.

BACKGROUND: Panic attacks, the hallmark of panic disorder, are often characterized by hyperventilation. Existing animal models of anxiety have not addressed the effects of the hyperventilation on anxiety-related behaviors. Doxapram is a respiratory stimulant that reliably evokes panic attacks in patients with panic disorder. We examined doxapram in four rodent models of anxiety and sought to identify brain regions involved in its behavioral effects. METHODS: The effects of doxapram were determined for cue and contextual fear conditioning, the open field test, and the social interaction test. The effect of doxapram on c-Fos-like immunoreactivity was examined in three brain regions. RESULTS: Doxapram at 4 mg/kg increased anxiety-related behaviors in all four anxiety models. An inverted U-shaped dose-response curve was identified for fear conditioning to cue. Doxapram induced c-Fos-like immunoreactivity in the central nucleus of the amygdala but not the lateral nucleus or the nucleus tractus solitarius. CONCLUSIONS: Doxapram enhanced anxiety-related behaviors in four animal models of anxiety that involve conditioning or spontaneous avoidance. The effect of doxapram may result from activation of neurons in the amygdala. Doxapram, by inducing hyperventilation, may be a useful adjunct to existing animal anxiety models for improving validity for panic anxiety.