Metaanálisis de los estudios publicados sobre alteraciones de los valores de las citocinas en la esquizofrenia: efectos del estado clínico y de los antipsicóticos / Meta-analysis of cytokine alterations in schizophrenia: clinical status and antipsychotic effects

Fundamento. La esquizofrenia se asocia con una disfunción del sistema inmunitario, incluidos valores aberrantes de citocinas. Efectuamos un metaanálisis de estas asociaciones, con una consideración de los efectos del estado clínico y el tratamiento antipsicótico tras la exacerbación aguda de la enfermedad. Métodos. Identificamos los artículos mediante una búsqueda en las bases de datos PubMed, PsychInfo e Institute for Scientific Information y las listas bibliográficas de los estudios identificados. Resultados. Cumplieron los criterios de inclusión 40 estudios. Los tamaños del efecto fueron similares para los estudios de pacientes hospitalizados con una recidiva aguda (RA) y un primer episodio de psicosis (PEP). La interleucina (IL)-1Beta, la IL-6 y el factor de crecimiento transformante Beta (TGF-Beta) parecieron ser marcadores del estado, ya que aumentaron en pacientes con RA y PEP (p<0,001 para cada uno) y se normalizaron con el tratamiento antipsicótico (p<0,001, p=0,008, y p=0,005, respectivamente). En comparación, la IL-12, el interferón gamma (IFN-gamma), el factor de necrosis tumoral alfa (TGF-alpha) y el receptor soluble de IL-2 (sIL-2R) parecieron ser marcadores de rasgo, ya que los valores se mantuvieron elevados en las exacerbaciones agudas y tras el tratamiento antipsicótico. No hubo diferencias de los valores de IL-6 entre pacientes ambulatorios medicados, estables e individuos de control (p=0,69). En el líquido cefalorraquídeo, los valores de IL-1Beta disminuyeron significativamente en pacientes con esquizofrenia en comparación con individuos de control (p=0,01). Conclusiones. Los tamaños del efecto similares en pacientes con RA y PEP indican que la asociación entre las anomalías de las citocinas y las exacerbaciones agudas de la esquizofrenia es independiente de la medicación antipsicótica. Mientras que algunas citocinas (IL-1β, IL-6 y TGF-β) podrían ser marcadores del estado para las exacerbaciones agudas, otras (IL-12, IFN-gamma, TNF-alpha y sIL-2R) podrían ser marcadores de rasgo. Aunque estos resultados podrían proporcionar la base para probar futuras hipótesis, la mayoría de estudios no controlaron los posibles factores de confusión, como el índice de masa corporal y el tabaquismo (AU)

Background. Schizophrenia is associated with immune system dysfunction, including aberrant cytokine levels. We performed a meta-analysis of these associations, considering effects of clinical status and antipsychotic treatment following an acute illness exacerbation. Methods. We identified articles by searching PubMed, PsychInfo, and Institute for Scientific Information and the reference lists of identified studies. Results. Forty studies met the inclusion criteria. Effect sizes were similar for studies of acutely relapsed inpatients (AR) and first-episode psychosis (FEP). Interleukin (IL)-1Beta, IL-6, and transforming growth factor-Beta (TGF-Beta) appeared to be state markers, as they were increased in AR and FEP (p<.001 for each) and normalized with antipsychotic treatment (p<.001, p=.008, and p=.005, respectively). In contrast, IL-12, interferon-γ (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha), and soluble IL-2 receptor (sIL-2R) appeared to be trait markers, as levels remained elevated in acute exacerbations and following antipsychotic treatment. There was no difference in IL-6 levels between stable medicated outpatients and control subjects (p=.69). In the cerebrospinal fluid, IL-1Beta was significantly decreased in schizophrenia versus controls (p=.01). Conclusions. Similar effect sizes in AR and FEP suggest that the association between cytokine abnormalities and acute exacerbations of schizophrenia is independent of antipsychotic medications. While some cytokines (IL-1Beta, IL-6, and TGF-Beta) may be state markers for acute exacerbations, others (IL-12, IFN-gamma, TNF-alpha, and sIL-2R) may be trait markers. Although these results could provide the basis for future hypothesis testing, most studies did not control for potential confounding factors such as body mass index and smoking (AU)

Meta-analysis of cytokine alterations in schizophrenia: clinical status and antipsychotic effects.

BACKGROUND: Schizophrenia is associated with immune system dysfunction, including aberrant cytokine levels. We performed a meta-analysis of these associations, considering effects of clinical status and antipsychotic treatment following an acute illness exacerbation. METHODS: We identified articles by searching PubMed, PsychInfo, and Institute for Scientific Information and the reference lists of identified studies. RESULTS: Forty studies met the inclusion criteria. Effect sizes were similar for studies of acutely relapsed inpatients (AR) and first-episode psychosis (FEP). Interleukin (IL)-1ß, IL-6, and transforming growth factor-ß (TGF-ß) appeared to be state markers, as they were increased in AR and FEP (p < .001 for each) and normalized with antipsychotic treatment (p < .001, p = .008, and p = .005, respectively). In contrast, IL-12, interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α), and soluble IL-2 receptor (sIL-2R) appeared to be trait markers, as levels remained elevated in acute exacerbations and following antipsychotic treatment. There was no difference in IL-6 levels between stable medicated outpatients and control subjects (p = .69). In the cerebrospinal fluid, IL-1ß was significantly decreased in schizophrenia versus controls (p = .01). CONCLUSIONS: Similar effect sizes in AR and FEP suggest that the association between cytokine abnormalities and acute exacerbations of schizophrenia is independent of antipsychotic medications. While some cytokines (IL-1ß, IL-6, and TGF-ß) may be state markers for acute exacerbations, others (IL-12, IFN-γ, TNF-α, and sIL-2R) may be trait markers. Although these results could provide the basis for future hypothesis testing, most studies did not control for potential confounding factors such as body mass index and smoking.

Utility of positron emission tomography-computed tomography in identification of residual nodal disease after chemoradiation for advanced head and neck cancer.

OBJECTIVES: Planned neck dissection after chemoradiation (CR) is often advocated in patients with head and neck squamous cell cancer (HNSCC) with advanced nodal disease who demonstrate a clinical complete response to CR because identification of residual occult nodal disease is difficult. We sought to investigate the utility of positron emission tomography-computed tomography (PET-CT) in identifying patients with occult nodal disease after CR. STUDY DESIGN: Nonrandomized retrospective cohort analysis. MATERIALS AND METHODS: The medical records of all patients treated with primary CR for advanced HNSCC with N2 or N3 disease from December 2003 to June 2005 were reviewed. Patients with a clinical complete response were eligible for inclusion if PET-CT performed at 8 to 10 weeks after CR showed no evidence of distant disease and they were treated with a planned neck dissection. RESULTS: Seventeen patients met study criteria. PET-CT was positive for residual nodal disease in 11 (64.7%) patients, with a standardized uptake value (SUV) range of 1.7 to 3.8. Pathologic examination revealed residual viable carcinoma in five (29.4%) patients, with tumor size ranging from 2.0 to 9.5 mm. Carcinoma was present in 2 of 11 (18.2%) patients with positive PET-CT scans and 3 of 6 (50%) patients with negative PET-CT scans. The sensitivity and specificity of PET-CT in predicting occult nodal disease was 40% and 25%, respectively. There was no correlation between PET-CT findings and histologic findings (P = .26) or between SUV and size of viable tumor (P = .67). CONCLUSIONS: A significant proportion of HNSCC patients with advanced neck disease harbor residual occult metastases after CR. PET-CT is not sufficiently specific or sensitive to reliably predict the need for posttreatment neck dissection.