Pro-/anti-inflammatory dysregulation in patients with first episode of psychosis: toward an integrative inflammatory hypothesis of schizophrenia.

BACKGROUND: Schizophrenia is a chronic syndrome of unknown etiology, predominantly defined by signs of psychosis. The onset of the disorder occurs typically in late adolescence or early adulthood. Efforts to study pathophysiological mechanisms in early stages of the disease are crucial in order to prompt intervention. METHODS: Case-control study of first-episode psychotic (FEP) patients and matched controls. We recruited 117 patients during the first year after their FEP according to the DSM-IV criteria and recruited 106 gender-, race-, and age-matched controls between September 2010 and June 2011. RESULTS: Biochemical studies carried out in peripheral mononuclear blood cells (PMBC) and plasma evidence a significant increase in intracellular components of a main proinflammatory pathway, along with a significant decrease in the anti-inflammatory ones. Multivariate logistic regression analyses identified the expression of inducible isoforms of nitric oxide synthase and cyclooxygenase in PMBC and homocysteine plasma levels as the most reliable potential risk factors and the inhibitor of the inflammatory transcription factor NFκB, IκBα, and the anti-inflammatory prostaglandin 15d-PGJ2 as potential protection factors. DISCUSSION: Taken as a whole, the results of this study indicate robust phenotypical differences at the cellular machinery level in PMBC of patients with FEP. Although more scientific evidence is needed, the determination of multiple components of pro- and anti-inflammatory cellular pathways including the activity of nuclear receptors has interesting potential as biological markers and potential risk/protective factors for FEP. Due to its soluble nature, a notable finding in this study is that the anti-inflammatory mediator 15d-PGJ2 might be used as plasmatic biomarker for first episodes of psychosis.

“Depressive co-morbidity in medical in-patients at the time of hospital discharge and outcome in a Primary Care follow-up. I. Rational and design of the project”

Objectives: In a context of a “continuity of care” model in Psychosomatic and Liaison Psychiatry, this study is intended to test, in patients to be discharged from Medicine wards, hypotheses related to a high prevalence of depression and, in particular, its negative outcome at six-months follow-up in Primary Care (PC), especially among the elderly. Methods: Sample. Consecutive patients aged 18 years or more, hospitalized in Medicine wards were randomly selected for screening at the time of admission. On the bases of a previous study and the expected sampling errors, sample size was estimated in 700patients (approximately 60% in geriatric age) for the initial screening, to recruit 75 or more cases of depression and enough number of control, non-cases without psychiatric morbidity..Instruments. Standardized, Spanish versions of screening/case-finding instruments COMPRI/INTERMED, Mini-Mental, CAGE and drug screening, Hospital Anxiety and Depression Scale (HADS), Standardized Polyvalent Psychiatric Interview (SPPI). Diagnostic criteria ICD-10 research, medical patients version and DSM-IV-TR (psychiatric);and ICD-9-M; ICHPPC, WONCA (medical). Cumulative Illness Rating Scale (CIRS)(severity of physical condition); SF36 and EuroQol (quality of life); Client Service Receipt Interview (CSRI) (costs).Procedure. Part I, hospital study: Two-phase screening (lay interviewers: COMPRI/INTERMED at admission; Mini-Mental, CAGE, HADS at the time of discharge; and standardized clinicians: SPPI). CIRS was used to control severity of physical conditions. Part II, follow-up study in PC (six months): Standardized clinicians, blind to the previous phases (HADS and SPPI to both cases and controls). Outcome study: Euro-Quol, SF36, CSRI and data on morbidity and mortality, were collected. Conclusions. To our knowledge, this is the first study using modern epidemiological methods in medical patients to be discharged with co-morbid depression and followed in PC with a “continuity of care” strategy. The final analysis of data should support the design of an evidence-based, intervention study on co-morbid depression (AU)