Leticia González-Blanco

Meta-analysis of glucose tolerance, insulin, and insulin resistance in antipsychotic-naïve patients with nonaffective psychosis

BACKGROUND Some studies have suggested that antipsychotic-naïve patients with nonaffective psychosis (NAP) have glucose intolerance. AIMS To conduct a systematic review and meta-analysis of fasting glucose (FG), two hour values in the oral glucose tolerance test (2HG), fasting insulin concentration (INS), and insulin resistance (IR). METHOD We identified possibly relevant studies, then selected studies, following usual guidelines, with two authors reviewing the manuscripts. We required studies to include subjects with nonaffective psychosis and control subjects. RESULTS There were 911 patients and 870 control subjects in the analysis of FG; their average ages were respectively 28.7 and 29.5years. Significant differences were found for all four variables, with effect size estimates ranging from 0.21 to 0.58. CONCLUSIONS As a group, at the time of first clinical contact for psychosis, people with NAP have a slight increase in FG, which most of them maintain in the normal range despite a small increase in IR by secreting additional INS. When faced with a physiological challenge such as a glucose tolerance test or antipsychotics, they are no longer able to maintain a normal glucose concentration.

Prolactin concentrations in antipsychotic-naïve patients with schizophrenia and related disorders: A meta-analysis

OBJECTIVE The use of dopaminergic antagonist antipsychotics is associated with hyperprolactinemia, but some studies have found increased prolactin concentrations in antipsychotic-naive patients with schizophrenia and related disorders. We conducted a systematic review and meta-analysis of studies of prolactin in antipsychotic-naïve patient with these disorders (PRISMA No. CRD42015016337). DATA SOURCES PubMed (Medline), PsycInfo, and Web of Science were searched for articles from 1950 to the present in English. STUDY SELECTION Seven studies of males (N=141 for patients, N=191 for control subjects) and five studies of females (N=67 and N=116) met criteria for inclusion: data on blood prolactin concentrations for both control subjects and antipsychotic-naive patients with schizophrenia or a related disorder, with data available separately for males and females. DATA EXTRACTION Data was extracted from the papers by one author and independently verified by a second. RESULTS The mean effect size for males was 1.02 (95% CI, 0.77, 1.26; p<0.001) and 0.43 for females (95% CI 0.11, 0.76; p<0.01). Meta-regression analyses for age, smoking, body mass index (BMI), year of publication, and cortisol were not significant. Funnel plots did not suggest the presence of a publication bias. CONCLUSIONS Our meta-analyses found significantly increased prolactin levels in both male and female antipsychotic-naïve patients with schizophrenia and related disorders. The small number of studies and limited matching for potentially confounding variables in some of the studies were limitations of this analysis. Prolonged hyperprolactinemia may lead to sexual dysfunction and osteoporosis, and some antipsychotics cause additional elevation of prolactin concentrations.

Biomarcadores sanguíneos diferenciales de las dimensiones psicopatológicas de la esquizofrenia

Symptomatology of schizophrenia is heterogeneous, there is not any pathognomonic symptom. Moreover, the diagnosis is difficult, since it is based on subjective information, instead of markers. The purpose of this study is to provide a review of the current status of blood-based biomarkers of psychopathological dimensions of schizophrenia. Inflammatory, hormonal or metabolic dysfunctions have been identified in patients with schizophrenia and it has attempted to establish biomarkers responsible for these dysfunctions. The identification of these biomarkers could contribute to the diagnosis and treatment of schizophrenia.

Regulation of inflammatory pathways in schizophrenia: A comparative study with bipolar disorder and healthy controls

BACKGROUND Immune-inflammatory processes have been implicated in schizophrenia (SCH), but their specificity is not clear. MAIN AIM To identify potential differential intra-/intercellular biochemical pathways controlling immune-inflammatory response and their oxidative-nitrosative impact on SCH patients, compared with bipolar disorder (BD) patients and healthy controls (HC). METHODS Cross-sectional, naturalistic study of a cohort of SCH patients (n=123) and their controls [BD (n=102) and HC (n=80)]. STATISTICAL ANALYSIS ANCOVA (or Quade test) controlling for age and gender when comparing the three groups, and controlling for age, gender, length of illness, cigarettes per day, and body mass index (BMI) when comparing SCH and BD. RESULTS Pro-inflammatory biomarkers: Expression of COX-1 was statistically higher in SCH and BD than HC (P<0.0001; P<0.0001); NFκB and PGE2 were statistically higher in SCH compared with BD (P=0.001; P<0.0001) and HC (P=0.003; P<0.0001); NLRP3 was higher in BD than HC (P=0.005); and CPR showed a gradient among the three groups. Anti-inflammatory biomarkers: BD patients had lower PPARγ and higher 15d-PGJ2 levels than SCH (P=0.005; P=0.008) and HC (P=0.001; P=0.001). Differences between SCH and BD: previous markers of SCH (NFκB and PGE2) and BD (PPARγ and 15d-PGJ2) remained statistically significant and, interestingly, iNOS and COX-2 (pro-inflammatory biomarkers) levels were statistically higher in SCH than BD (P=0.019; P=0.040). CONCLUSIONS This study suggests a specific immune-inflammatory biomarker pattern for established SCH (NFκB, PGE2, iNOS, and COX-2) that differentiates it from BD and HC. In future, their pharmacological modulation may constitute a promising therapeutic target.

Protocolo de estudio de un programa para la prevención de la recurrencia del comportamiento suicida basado en el manejo de casos (PSyMAC)

INTRODUCTION Prevention of suicidal behaviour is a public health priority in the European Union. A previous suicide attempt is the best risk predictor for future attempts, as well as completed suicides. The primary aim of this article is to describe a controlled study protocol designed for prevention of recurrent suicidal behaviour that proposes case management, and includes a psychoeducation program, as compared with the standard intervention (PSyMAC). METHODS Patients admitted from January 2011 to June 2013 to the emergency room of the Hospital Universitario Central de Asturias were evaluated using a protocol including sociodemographic, psychiatric, and psychosocial assessment. Patients were randomly assigned to either a group receiving continuous case management including participation in a psychoeducation program (experimental group), or a control group receiving standard care. The primary objective is to examine whether or not the period of time until recurrent suicidal behaviour in the experimental group is significantly different from that of the control group. CONCLUSION PSyMAC proposes low cost and easily adaptable interventions to the usual clinical setting that can help to compensate the shortcoming of specific action protocols and suicidal behaviour prevention programs in our country. The evaluation of PSyMAC results will determine their real effectivity as a case-magament program to reduce suicidal risk.

Early versus late stage schizophrenia. What markers make the difference

Abstract Objectives: To identify the psychopathological, cognitive, functional, physical health and inflammatory markers that differentiate between early-stage schizophrenia (ESSCH) and late-stage schizophrenia (LSSCH). Methods: Cross-sectional, naturalistic study of 104 patients with SCH. The sample was divided in two groups: 35 ESSCH (≤7 years’ duration of illness) and 69 LSSCH (>10 years’ duration of illness). Statistical analysis: chi-square test and Students t-test and ANCOVA (or Quade test) controlling for age, sex, BMI and number of cigarettes/day. Finally, a binomial logistic regression was made. Results: ESSCH show greater negative symptom severity (t = 2.465, p = 0.015), lower levels of IκBα (F = 7.644, p = 0.007), were more frequently classified as normal weight (40% vs 18.8%, p = 0.032) compared with LSSCH. The binomial logistic regression model included age (B = 0.127, p = 0.001) and IκBα (B = 0.025, p = 0.002) and accounted for 38.9% of the variance (model df =7, chi-square =41.841, p < 0.0001). Conclusions: Age and IκBα are the unique markers that differentiate between ESSCH patients whose duration of illness is less than 7 years and LSSCH patients. These results support the hypothesis of toxicity of episodes and highlight the importance of preventing new episodes.

T17. OXIDATIVE STRESS BIOMARKERS AND NEGATIVE DIMENSION IN THE FIRST TEN YEARS OF SCHIZOPHRENIA: A 1-YEAR FOLLOW-UP STUDY

Abstract Background Several studies have documented changes in oxidative parameters and antioxidant enzymes in patients with schizophrenia (1, 2). However, their relation to negative symptoms and the longitudinal clinical course is still unclear. The objectives of the present study are to: 1) analyze the association between oxidative stress biomarkers and negative dimension; 2) identify if these biomarkers could predict clinical outcomes in stable patients with schizophrenia at 1-year follow-up. Methods A 1-year follow-up study of 57 stable outpatients with schizophrenia (≤10 years of illness) (mean age=31.5 ± 6.5; 63.2% males). Assessment PANSS, Clinical Assessment Interview of Negative Symptoms (CAINS) -Motivation/Pleasure (MAP) & Expression (EXP) domains-, Brief Negative Symptom Scale (BNSS). Oxidative stress biomarkers: homocysteine, hemolysis test (% hemolysis), lipid peroxidation subproducts (LPO), catalase activity in erythrocytes (CAT). Pearson correlations were performed to determine associations between biomarkers and clinical scores at baseline, and they were included in stepwise multiple linear regression analyses, considering potential confounding factors. The clinical course for each psychopathological domain was determined using the formula: [follow-up-baseline scores]. Positive values were interpreted as worsening, while negative improvement. Pearson correlation and multiple linear regression analyses were performed to determine if baseline levels of oxidative stress parameters were predictors of clinical changes at follow-up. Results 1) Baseline associations: Final regression models identified that LPO level was a significant predictor of lower scores in PANSS-N, BNSS total, Avolition and Blunted Affect subscale of BNSS and CAINS-EXP (β= -0.408; -0.290, -0.254, -0.296, -0.247, respectively). 2) Longitudinal course: At 1-year follow-up, patients only improved significantly (p<0.05) in PANSS-Total [59.4 ± 16.4 - 54.5 ± 16.0 (t=3.362)], PANSS-General [29.7 ± 8.9 - 26.9 ± 7.9 (t=3.362)], Blunted Affect subscale [6.9 ± 5.0 - 5.9 ± 4.7 (t=2.489)], and almost significant (p<0.069) in CAINS-EXP and BNSS total score. No significant changes in BMI, waist circumference, smoking or antipsychotic equivalent doses were detected, but they were also considered in regression analyses. A higher percentage of hemolysis at baseline, with a decrease in equivalent doses of antipsychotics, both significantly predict an improvement in scores of PANSS-N (R2=0.140, F=7.166), BNSS (R2=0.246, F=6.193) and CAINS-EXP (R2=0.186, F=5.259). Discussion Lower concentrations of LPO were related to greater severity of negative symptoms as avolition and blunted affect (inner world). Longitudinal analyses showed that higher % of hemolysis at baseline predict an improvement of negative dimension at 1-year follow-up. From our results, we hypothesize that there is an inverse relationship between oxidative stress and negative dimension in stable patients with schizophrenia during the first ten years of illness.

Biomarcadores de estrés oxidativo y dimensiones clínicas en los 10 primeros años de esquizofrenia

INTRODUCTION Several studies have described increased oxidative stress parameters in patients with schizophrenia. The objectives of the current study were to identify potential oxidative stress biomarkers in stable patients during first 10 years of schizophrenia and determine if they are associated with specific clinical dimensions. MATERIAL AND METHODS Seventy-three clinically stable outpatients with schizophrenia and 73 sex and age-matched healthy controls were recruited. Sociodemographic, clinical and biological data were collected at enrollment. Blood biomarkers included homocysteine, the percentage of hemolysis, lipid peroxidation subproducts, and as an antioxidant biomarker, catalase activity in erythrocytes. RESULTS Comparative analyses after controlling for smoking and metabolic syndrome evidenced a significant increase in catalase activity in patients. Also, lower lipid peroxidation levels showed an association with negative symptoms. CONCLUSIONS In conclusion, compensatory antioxidant mechanisms might be increased in stable patients with schizophrenia at early stages. Furthermore, there may be an inverse relationship between oxidative stress and negative dimension.

¿Pueden ser la interleucina-2 y la interleucina-1β biomarcadores específicos

INTRODUCTION Evidence suggests the existence of cytokine disturbances in patients with schizophrenia but their association with psychopathology is still unclear. The aim of the current study was to determine if pro-inflammatory cytokine levels (tumor necrosis factor-α, interleukin (IL)-6, IL-2, IL-1β, IL-1RA) are increased in stable outpatients compared with healthy subjects, and to analyze if they could be specific biomarkers of clinical dimensions in schizophrenia. METHODS We studied 73 stable outpatients with schizophrenia in their first 10 years of illness and 73 age- and sex-matched healthy controls. An accurate assessment of clinical dimensions (positive, negative, depressive, cognitive) was performed in patients. RESULTS Only IL-6 levels were significantly increased in patients after controlling for body mass index, waist circumference, smoking, and psychopharmacological treatment, compared with healthy subjects. After adjusting for several confounders, multiple linear regression models identified that Positive and Negative Syndrome Scale negative symptoms, general psychopathology, and global severity are predicted by IL-1β concentrations, while motivation and pleasure domain of Clinical Assessment Interview for Negative Symptoms and Personal and Social Performance global functioning scores are predicted by IL-2 levels. Cognitive performance, positive, and depressive symptom severity did not correlate with any cytokine. CONCLUSIONS Our findings suggested that IL-6 concentrations are elevated in stable patients with schizophrenia. Whereas IL-2 specifically marks severity of the motivation and pleasure domain of negative symptoms, IL-1β is not specific to this dimension as it also predicts severity of general and global symptomatology.

Estadificación clínica en los trastornos mentales graves: trastorno bipolar, depresión y esquizofrenia

Clinical staging is a diagnostic tool used in other medical specialties, which has resulted from the combination of a categorical and dimensional approach. In the last 2decades, the usefulness of its application in the field of psychiatry has been suggested, mainly as a tool for diagnostic help, and therapeutic and prognostic orientation. In this paper we review the clinical staging models that have been proposed to date for bipolar disorder, depression and schizophrenia. A literature search was performed in PubMed and Medline databases. A total of 15 studies were selected according to inclusion and exclusion criteria. Models were grouped according to the type of disorder for which staging was proposed (bipolar disorder: 4, depression: 5, schizophrenia: 6), and their characteristics were described. As a conclusion, we identify the need to empirically validate these models to demonstrate that staging is a useful tool for clinical practice.