A Network Comprised of miR-15b and miR-29a Is Involved in Vascular Endothelial Growth Factor Pathway Regulation in Thymus Adipose Tissue from Elderly Ischemic Cardiomyopathy Subjects.

As the human thymus ages, it undergoes a transformation into adipose tissue known as TAT. Interestingly, in previous research, we observed elevated levels of vascular endothelial growth factor A (VEGFA) in TAT from patients with ischemic cardiomyopathy (IC), particularly in those over 70 years old. Moreover, in contrast to subcutaneous adipose tissue (SAT), TAT in elderly individuals exhibits enhanced angiogenic properties and the ability to stimulate tube formation. This makes TAT a promising candidate for angiogenic therapies and the regeneration of ischemic tissues following coronary surgery. MicroRNAs (miRNAs) have emerged as attractive therapeutic targets, especially those that regulate angiogenic processes. The study's purpose is to determine the miRNA network associated with both the VEGFA pathway regulation and the enrichment of age-linked angiogenesis in the TAT. RT-PCR was used to analyze angiogenic miRNAs and the expression levels of their predicted target genes in both TAT and SAT from elderly and middle-aged patients treated with coronary artery bypass graft surgery. miRTargetLink Human was used to search for miRNAs and their target genes. PANTHER was used to annotate the biological processes of the predicted targets. The expression of miR-15b-5p and miR-29a-3p was significantly upregulated in the TAT of elderly compared with middle-aged patients. Interestingly, VEGFA and other angiogenic targets were significantly upregulated in the TAT of elderly patients. Specifically: JAG1, PDGFC, VEGFA, FGF2, KDR, NOTCH2, FOS, PDGFRA, PDGFRB, and RHOB were upregulated, while PIK3CG and WNT7A were downregulated. Our results provide strong evidence of a miRNA/mRNA interaction network linked with age-associated TAT angiogenic enrichment in patients with IC.

The Impact of Stressful Life Events on Suicidal Ideation in Gender Dysphoria: A Moderator Effect of Perceived Social Support.

Factors associated with suicidal ideation in the gender dysphoria population are not completely understood. This high-risk population is more likely to suffer stressful events such as assault or employment discrimination. This study aimed to determine the association of stressful events and social support on suicidal ideation in gender dysphoria and to analyze the moderator effect of social support in relation to stressful events and suicidal ideation. A cross-sectional design was used in a clinical sample attending a public gender identity unit in Spain that consisted of 204 individuals (51.7% birth-assigned males and 48.3% birth-assigned females), aged between 13 and 59 (M = 27.95 years, SD = 9.58). A Structured Clinical Interview, a list of 16 stressful events, and a functional social support questionnaire (Duke-UNC-11) were used during the initial visits to the unit. The data were collected between 2011 and 2012. A total of 50.1% of the sample have had suicidal ideation. The following stressful events were associated with suicidal ideation: homelessness, eviction from home, and having suffered from physical or verbal aggression. Also, there was an inverse relation between perceived social support and suicidal ideation. There was a statistically significant interaction between a specific stressful event (eviction) and perceived social support. The study suggests that the promotion of safer environments could be related to lower suicidal ideation and that networks that provide social support could buffer the association between specific stressful events and suicidal ideation.

Pigment epithelium-derived factor (PEDF) and PEDF-receptor in the adult mouse brain: Differential spatial/temporal localization pattern.

Pigment epithelium-derived factor (PEDF) is a multifunctional protein which was initially described in the retina, although it is also present in other tissues. It functions as an antioxidant agent promoting neuronal survival. Recently, a PEDF receptor has shown an elevated binding affinity for PEDF. There are no relevant data regarding the distribution of both proteins in the brain, therefore the main goal of this work was to investigate the spatiotemporal presence of PEDF and PEDFR in the adult mouse brain, and to determine the PEDF blood level in mouse and human. The localization of both proteins was analyzed by different experimental methods such as immunohistochemistry, western-blotting, and also by enzyme-linked immunosorbent assay. Differential expression was found in some telencephalic structures and positive signals for both proteins were detected in the cerebellum. The magnitude of the PEDFR labeling pattern was higher than PEDF and included some cortical and subventricular areas. Age-dependent changes in intensity of both protein immunoreactions were found in the cortical and hippocampal areas with greater reactivity between 4 and 8 months of age, whilst others, like the subventricular zones, these differences were more evident for PEDFR. Although ubiquitous presence was not found in the brain for these two proteins, their relevant functions must not be underestimated. It has been described that PEDF plays an important role in neuroprotection and data provided in the present work represents the first extensive study to understand the relevance of these two proteins in specific brain areas.

Illness Insight and Medication Adherence Among Patients With Bipolar Disorder.

The aim of this study was to investigate the factors associated with illness insight and medication adherence in bipolar disorder (BD). This is a cross-sectional study (with a retrospective evaluation of longitudinal variables) and a secondary analysis of a BD database. The insight of 108 outpatients (age, 48.2 ± 14.1 years, 69% women, 33% euthymic) was measured with three items of the Association of Methodology and Documentation in Psychiatry scale. Their adherence was assessed through patients' and caregivers' reports, plus serum levels. We performed multivariate logistic regression analyses. Full insight was independently and directly associated with adherence, a social support score, and depressive symptoms and inversely associated with intensity of manic symptoms, problems ever with alcohol, and age at onset of the first symptoms. Medication adherence was independently and directly associated with insight, being married, and having had a psychiatric hospitalization and inversely with having suffered a high number of depressive episodes, intensity of manic symptoms, and heavy tobacco smoking.

Psychometric Properties of the Frost Multidimensional Perfectionism Scale in Spanish Children and Adolescents.

The Frost Multidimensional Perfectionism Scale (FMPS) is one of the most used instruments to assess perfectionism. The FMPS assesses six dimensions: Concern over Mistakes (CM), Parental Expectations (EP), Parental Criticism (PC), Doubts about Actions (DA), Organization (OR), and Personal Standards (PS). CM, PE, PC, and DA are facets of a more general dimension considered Maladaptive Perfectionism. PS is frequently considered Adaptive Perfectionism. FMPS psychometric properties have been studied in adults but scarcely in children. We adapted the FMPS for Spanish children and adolescents and studied these properties in a sample of 1,648 Spanish young people (mean age = 13.36; SD = 2.28). Multigroup confirmatory factor analyses were used to test whether the FMPS dimensions found in adults are applicable to children. Results supported this hypothesis. The FMPS dimensional structure was invariant across gender and age. FMPS subscales showed good internal consistency (Cronbach's α: .71-.92) and test-retest reliability (intraclass correlations: .70-.85). Moderate and high correlations with measures of dysfunctional beliefs, anxiety, and depression supported the validity of the FMPS scores. Results from regression equations showed that the relationship of perfectionism with anxiety and depression is mostly due to Maladaptive Perfectionism.

Inflammatory gene expression in adipose tissue according to diagnosis of anxiety and mood disorders in obese and non-obese subjects.

Psychiatric disorders have been widely reported to be associated with systemic inflammation upregulation and adiposity. However, there are no data that link adipose tissue inflammation to these mental disorders. The analysis of adipokines and inflammation-related markers in adipose tissue could help to elucidate the potential association between obesity and mental health. An observational study was conducted in samples of patients consisting of non-obese and obese subjects, who were diagnosed with anxiety or mood disorders. Gene expression of adiponectin (ADIPOQ), leptin (LEP) and inflammatory markers (IL6, IL1B, TNF, CCL2, CSF3, ITGAM, and PLAUR) were determined in visceral (VAT) and subcutaneous (SAT) adipose tissues. Our results showed that the gene expression of adipokines and inflammation-related markers was higher in the VAT and SAT of obese subjects compared with non-obese subjects. Regarding mental disorders, all the inflammatory genes in the VAT were significantly higher in non-obese subjects with anxiety or mood disorders than in subjects without mental disorders, except for TNF and ITGAM. Additionally, IL6 expression was significantly lower in SAT. In contrast, obese patients diagnosed with anxiety or mood disorders only showed significantly lower expression levels of IL1B in VAT and ADIPOQ in SAT when compared with obese subjects without mental disorders. These data suggest the potential involvement of VAT inflammation in anxiety and mood disorders, involving complex mechanisms which are strongly affected by obesity.

Patients Admitted to Three Spanish Intensive Care Units for Poisoning: Type of Poisoning, Mortality, and Functioning of Prognostic Scores Commonly Used.

Objectives. To evaluate the gravity and mortality of those patients admitted to the intensive care unit for poisoning. Also, the applicability and predicted capacity of prognostic scales most frequently used in ICU must be evaluated. Methods. Multicentre study between 2008 and 2013 on all patients admitted for poisoning. Results. The results are from 119 patients. The causes of poisoning were medication, 92 patients (77.3%), caustics, 11 (9.2%), and alcohol, 20 (16,8%). 78.3% attempted suicides. Mean age was 44.42 ± 13.85 years. 72.5% had a Glasgow Coma Scale (GCS) ≤8 points. The ICU mortality was 5.9% and the hospital mortality was 6.7%. The mortality from caustic poisoning was 54.5%, and it was 1.9% for noncaustic poisoning (p < 0.001). After adjusting for SAPS-3 (OR: 1.19 (1.02-1.39)) the mortality of patients who had ingested caustics was far higher than the rest (OR: 560.34 (11.64-26973.83)). There was considerable discrepancy between mortality predicted by SAPS-3 (26.8%) and observed (6.7%) (Hosmer-Lemeshow test: H = 35.10; p < 0.001). The APACHE-II (7,57%) and APACHE-III (8,15%) were no discrepancies. Conclusions. Admission to ICU for poisoning is rare in our country. Medication is the most frequent cause, but mortality of caustic poisoning is higher. APACHE-II and APACHE-III provide adequate predictions about mortality, while SAPS-3 tends to overestimate.

Gender Dysphoria and Social Anxiety: An Exploratory Study in Spain.

INTRODUCTION: Social anxiety in gender dysphoria is still under investigation. AIM: To determine the prevalence and associated factors of social anxiety in a sample of individuals with gender dysphoria. METHODS: A cross-sectional design was used in a clinical sample attending a public gender identity unit in Spain. The sample consisted of 210 individuals (48% trans female and 52% trans male). MAIN OUTCOME MEASURES: Mini-International Neuropsychiatric Interview (MINI) for diagnosis of social anxiety disorder, Structured Clinical Interview, Exposure to Violence Questionnaire (EVQ), Beck Depression Inventory (BDI-II), and Functional Social Support Questionnaire (Duke-UNC-11). RESULTS: Of the total sample, 31.4% had social anxiety disorder. Social anxiety disorder was highly correlated with age (r = -0.181; CI = 0.061-0.264; P = .009) and depression (r = 0.345; CI = 0.213-0.468; P < .001); it is strongly associated to current cannabis use (relative risk [RR] = 1.251; CI = 1.070-1.463; P = .001) and lifetime suicidal ideation (RR = 1.902; CI 1.286-2.814; P < .001). Moreover, it is significantly associated to lifetime nonsuicidal self-injury (RR = 1.188; CI 1.018-1.386; P = .011), nationality (RR = 7.792; CI 1.059-57.392; P = .013), perceived violence at school during childhood and adolescence (r = 0.169; CI = 0.036-0.303; P = .014), unemployment (RR = 1.333; CI 1.02-1.742; P = .021), and hospitalization of parents in childhood (RR = 1.146; CI = 1.003-4.419; P = .046). Using multivariable analysis, the highly significant variables within the model were depression score (odds ratio [OR] = 1.083; CI = 1.045-1.123; P < .001) and current cannabis use (OR = 3.873; CI = 1.534-9.779, P = .004), also age (OR = 0.948; CI = 0.909-0.989; P = .012), hospitalization of parents during childhood (OR = 2.618; CI = 1.107-6.189; P = .028), and nationality (OR = 9.427; CI = 1.065-83.457; P = .044) were associated with social anxiety disorder. CONCLUSION: This study highlights the necessity of implementing actions to prevent and treat social anxiety in this high-risk population.

An Abnormal Nitric Oxide Metabolism Contributes to Brain Oxidative Stress in the Mouse Model for the Fragile X Syndrome, a Possible Role in Intellectual Disability.

BACKGROUND: Fragile X syndrome is the most common genetic cause of mental disability. Although many research has been performed, the mechanism underlying the pathogenesis is unclear and needs further investigation. Oxidative stress played major roles in the syndrome. The aim was to investigate the nitric oxide metabolism, protein nitration level, the expression of NOS isoforms, and furthermore the activation of the nuclear factor NF-κB-p65 subunit in different brain areas on the fragile X mouse model. METHODS: This study involved adult male Fmr1-knockout and wild-type mice as controls. We detected nitric oxide metabolism and the activation of the nuclear factor NF-κBp65 subunit, comparing the mRNA expression and protein content of the three NOS isoforms in different brain areas. RESULTS: Fmr1-KO mice showed an abnormal nitric oxide metabolism and increased levels of protein tyrosine nitrosylation. Besides that, nuclear factor NF-κB-p65 and inducible nitric oxide synthase appeared significantly increased in the Fmr1-knockout mice. mRNA and protein levels of the neuronal nitric oxide synthase appeared significantly decreased in the knockout mice. However, the epithelial nitric oxide synthase isoform displayed no significant changes. CONCLUSIONS: These data suggest the potential involvement of an abnormal nitric oxide metabolism in the pathogenesis of the fragile X syndrome.

Sociodemographic Characteristics and Psychological Adjustment Among Transsexuals in Spain.

This study examined the sociodemographic characteristics and the psychological adjustment of transsexuals in Andalusia (Spain), and also analyzed the differences between female-to-male (FtM) and male-to-female (MtF) transsexuals. The sample included 197 transsexuals (101 MtF and 96 FtM) selected from those who visited the Transsexual and Gender Identity Unit at the Carlos Haya Hospital in Malaga between 2011 and 2012. Our analyses indicated that MtF transsexuals were more likely to have lower educational levels, live alone, have worked less frequently throughout their lifetime, and have engaged in prostitution. For FtM transsexuals, there were more frequent references to the mother's psychiatric history and more social avoidance and distress. Multivariate analysis showed that the number of personality dysfunctional traits and unemployment status were associated with depression in the entire sample. The following three conclusions can be made: there are significant differences between MtF and FtM transsexuals (mainly related to sociodemographic variables), depression was high in both groups, and a remarkable percentage of transsexuals have attempted suicide (22.8 %) or have had suicidal thoughts (52.3 %).

Oxidative stress and antioxidant parameters in patients with major depressive disorder compared to healthy controls before and after antidepressant treatment: results from a meta-analysis.

OBJECTIVE: To investigate the role of oxidative stress and antioxidants in depression. DATA SOURCES: We searched the literature without language restrictions through MEDLINE/PubMed, Cochrane Library, Fisterra, and Galenicom from database inception until December 31, 2013, supplemented by a hand search of relevant articles. Search terms included (1) oxidative stress, antioxidant*, nitrosative stress, nitrative stress, nitro-oxidative stress, free radical*, and names of individual oxidative stress markers/antioxidants and (2) depression and related disorders and antidepressant. STUDY SELECTION: Included were studies in patients with depression comparing antioxidant or oxidative stress markers with those in healthy controls before and after antidepressant treatment. DATA EXTRACTION: Two authors independently extracted the data for antioxidant or oxidative stress markers. Standardized mean differences (SMDs) ± 95% confidence intervals (CIs) for results from ≥ 3 studies were calculated. DATA SYNTHESIS: Altogether, 29 studies (N = 3,961; patients with depression = 2,477, healthy controls = 1,484) reported on the oxidative stress marker malondialdehyde (MDA) and total nitrites, the antioxidants uric acid and zinc, or the antioxidant-enhancing enzymes superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPX). When patients with depression were compared with healthy controls, depression was associated with higher oxidative stress MDA levels (8 studies; n = 916; SMD = 1.34; 95% CI, 0.57 to 2.11; P < .001), lower antioxidant uric acid (4 studies; n = 512; SMD = -0.64; 95% CI, -1.22 to -0.06; P = .030) and zinc levels (13 studies; n = 2,002; SMD = -0.66; 95% CI, -0.98 to -0.34; P < .0001), and higher antioxidant-enhancing enzyme SOD levels (11 studies; n = 902; SMD = 0.62; 95% CI, 0.07 to 1.17; P = .028), while differences in total nitrites and CAT and GPX were nonsignificant. Antidepressant treatment, which significantly reduced Hamilton Depression Rating Scale scores (24.6 ± 0.7 to 16.2 ± 1.6; SMD = 2.65; 95% CI, 1.13 to 4.15; P = .00065), reduced MDA (4 studies; n = 194; SMD = -1.45; 95% CI, -2.43 to -0.47; P = .004) and increased uric acid (3 studies; n = 212; SMD = 0.76; 95% CI, 0.03 to 1.49; P = .040) and zinc levels (3 studies; n = 65; SMD = 1.22; 95% CI, 0.40 to 2.04, P = .004), without differences in MDA (P = .60), uric acid (P = .10), and zinc (P = .163) levels compared to healthy controls. CONCLUSIONS: Results suggest that oxidative stress plays a role in depression and that antidepressant activity may be mediated via improving oxidative stress/antioxidant function.

Clusters de casos de suicidio espacio-temporal en la comunidad de Antequera (España) / Space-time suicide clustering in the community of Antequera (Spain)

Introducción. En España, cada año consuman suicidio alrededor de 3.500 personas. El principal objetivo del presente estudio fue examinar si eran evidentes agrupaciones (clusters) espacio-temporales de suicidio en la región de Antequera (Málaga, España). Métodos. Muestra y procedimiento. Entre el 1 de enero de 2004 y el 31 de diciembre de 2008, se identificaron todos los casos de suicidio consumado (fuente: Servicio de Patología Forense del Instituto de Medicina Legal, Málaga, España). Geolocalización. Usamos Google Earth para calcular las coordenadas del domicilio de todos los casos de suicidio. Análisis estadístico. Usamos el programa SaTScan® espacio-temporal y la función K de Ripley para examinar la presencia de agrupaciones (clusters) espacio-temporales de los casos de suicidio. Acto seguido, utilizamos la prueba de la X2 de Pearson para determinar la presencia de diferencias estadísticamente significativas entre los casos de suicidio identificados dentro y fuera de las agrupaciones de suicidio. Resultados. En los análisis del presente estudio efectuado en el municipio de Antequera, de un total de 120 individuos que cometieron suicidio se incluyeron 96 (80%). Se identificaron pruebas estadísticamente significativas para 7 agrupaciones espacio-temporales de suicidio dentro de los límites críticos de 0-2,5 km de distancia y durante la primera y segunda semana después del caso de suicidio (p < 0,05 en ambos casos). Entre los casos de suicidio dentro de agrupaciones (n = 17), no hubo ningún individuo en el que se hubiera establecido un diagnóstico de trastorno psicótico actual, mientras que, entre los casos de suicidio fuera de las agrupaciones espacio-temporales, en el 20%, se había establecido dicho diagnóstico (X2 = 4,13; gl = 1; p < 0,05). Conclusiones. En la región circundante de Antequera están presentes agrupaciones (clusters) espacio-temporales de los casos de suicidio. Entre pacientes con un diagnóstico de trastorno psicótico actual hubo menos probabilidades de una influencia por los factores que determinan las agrupaciones espacio-temporales de los casos de suicidio consumado (AU)

Introduction. Approximately 3,500 people commit suicide every year in Spain. The main aim of this study is to explore if a spatial and temporal clustering of suicide exists in the region of Antequera (Málaga, España). Methods. Sample and procedure: All suicides from January 1, 2004 to December 31, 2008 were identified using data from the Forensic Pathology Department of the Institute of Legal Medicine, Málaga (España). Geolocalisation. Google Earth was used to calculate the coordinates for each suicide decedent's address. Statistical analysis. A spatiotemporal permutation scan statistic and the Ripley's K function were used to explore spatiotemporal clustering. Pearson's chi-squared was used to determine whether there were differences between suicides inside and outside the spatiotemporal clusters. Results. A total of 120 individuals committed suicide within the region of Antequera, of which 96 (80%) were included in our analyses. Statistically significant evidence for 7 spatiotemporal suicide clusters emerged within critical limits for the 0-2.5 km distance and for the first and second semanas (P < .05 in both cases) after suicide. There was not a single subject diagnosed with a current psychotic disorder, among suicides within clusters, whereas outside clusters, 20% had this diagnosis (X2 = 4.13; df = 1; P < .05). Conclusions. There are spatiotemporal suicide clusters in the area surrounding Antequera. Patients diagnosed with current psychotic disorder are less likely to be influenced by the factors explaining suicide clustering (AU)

[Space-time suicide clustering in the community of Antequera (Spain)]. / Clusters de casos de suicidio espacio-temporal en la comunidad de Antequera (España).

INTRODUCTION: Approximately 3,500 people commit suicide every year in Spain. The main aim of this study is to explore if a spatial and temporal clustering of suicide exists in the region of Antequera (Málaga, España). METHODS: Sample and procedure: All suicides from January 1, 2004 to December 31, 2008 were identified using data from the Forensic Pathology Department of the Institute of Legal Medicine, Málaga (España). Geolocalisation. Google Earth was used to calculate the coordinates for each suicide decedent's address. Statistical analysis. A spatiotemporal permutation scan statistic and the Ripley's K function were used to explore spatiotemporal clustering. Pearson's chi-squared was used to determine whether there were differences between suicides inside and outside the spatiotemporal clusters. RESULTS: A total of 120 individuals committed suicide within the region of Antequera, of which 96 (80%) were included in our analyses. Statistically significant evidence for 7 spatiotemporal suicide clusters emerged within critical limits for the 0-2.5 km distance and for the first and second semanas (P<.05 in both cases) after suicide. There was not a single subject diagnosed with a current psychotic disorder, among suicides within clusters, whereas outside clusters, 20% had this diagnosis (X2=4.13; df=1; P<.05). CONCLUSIONS: There are spatiotemporal suicide clusters in the area surrounding Antequera. Patients diagnosed with current psychotic disorder are less likely to be influenced by the factors explaining suicide clustering.

Substance use and social anxiety in transsexual individuals.

OBJECTIVE: This study examined social anxiety and use of cannabis and cocaine among transsexuals. METHODS: A total of 379 transsexuals seeking treatment or consultation participated in this study, providing data on sociodemographics, substance use, and anxiety. Analyses were based on (a) lifetime but not current use versus never used and (b) current use only versus no current use (lifetime only or never used). RESULTS: Lifetime only cannabis users (n = 72, 19%) and lifetime only cocaine users (n = 36, 9.8%) were older, had more victimization, and received more mental health treatment that those who never used. Current cannabis users (n = 47, 12.4%) had higher scores on fear of negative evaluation and social avoidance than those not currently using (p <.01). Multivariate analysis showed that social avoidance and fear of negative evaluation were associated with current cannabis use (p <.05), but not cocaine. Further, being single was associated with current cannabis use, after controlling for social avoidance and fear of negative evaluation (p <.05). CONCLUSIONS: Transsexuals' levels of anxiety and cannabis/cocaine use are comparable to those in the general population. Cannabis may be used to control anxiety and can have detrimental clinical implications for transsexuals.

A combination of ascorbic acid and α-tocopherol to test the effectiveness and safety in the fragile X syndrome: study protocol for a phase II, randomized, placebo-controlled trial.

BACKGROUND: Fragile X syndrome (FXS) is an inherited neurodevelopmental condition characterised by behavioural, learning disabilities, physical and neurological symptoms. In addition, an important degree of comorbidity with autism is also present. Considered a rare disorder affecting both genders, it first becomes apparent during childhood with displays of language delay and behavioural symptoms.Main aim: To show whether the combination of 10 mg/kg/day of ascorbic acid (vitamin C) and 10 mg/kg/day of α-tocopherol (vitamin E) reduces FXS symptoms among male patients ages 6 to 18 years compared to placebo treatment, as measured on the standardized rating scales at baseline, and after 12 and 24 weeks of treatment.Secondary aims: To assess the safety of the treatment. To describe behavioural and cognitive changes revealed by the Developmental Behaviour Checklist Short Form (DBC-P24) and the Wechsler Intelligence Scale for Children-Revised. To describe metabolic changes revealed by blood analysis. To measure treatment impact at home and in an academic environment. METHODS/DESIGN: A phase II randomized, double-blind pilot clinical trial. SCOPE: male children and adolescents diagnosed with FXS, in accordance with a standardized molecular biology test, who met all the inclusion criteria and none of the exclusion criteria. INSTRUMENTATION: clinical data, blood analysis, Wechsler Intelligence Scale for Children-Revised, Conners parent and teacher rating scale scores and the DBC-P24 results will be obtained at the baseline (t0). Follow up examinations will take place at 12 weeks (t1) and 24 weeks (t2) of treatment. DISCUSSION: A limited number of clinical trials have been carried out on children with FXS, but more are necessary as current treatment possibilities are insufficient and often provoke side effects. In the present study, we sought to overcome possible methodological problems by conducting a phase II pilot study in order to calculate the relevant statistical parameters and determine the safety of the proposed treatment. The results will provide evidence to improve hyperactivity control and reduce behavioural and learning problems using ascorbic acid (vitamin C) and α-tocopherol (vitamin E). The study protocol was approved by the Regional Government Committee for Clinical Trials in Andalusia and the Spanish agency for drugs and health products. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01329770 (29 March 2011).

Phosphate levels as a possible state marker in panic disorder: preliminary study of a feasible laboratory measure for routine clinical practice.

OBJECTIVE: Low serum phosphate level is considered one of the metabolic adaptations to the respiratory alkalosis induced by hyperventilation associated with panic disorder. The aim of this study was to assess phosphatemia as a possible state marker for panic disorder. METHODS: Sixteen panic disorder patients underwent clinical assessment with a semi-structured interview, a set of rating scales and the self-rated State and Trait Anxiety Inventory (STAI), as well as extraction of venous blood samples at baseline and after 12 weeks of pharmacological treatment. Ten healthy volunteers of similar sex, age and educational level filled out the STAI and gave blood samples at baseline and 12 weeks later. RESULTS: The median (25th-75th percentiles) of phosphate levels (mg/dl) was 2.68 (2.22-3.18) among patients and 4.13 (3.74-4.70) among healthy volunteers respectively (P < 0.001). Seven (44%) patients and no healthy volunteers presented low serum phosphate (<2.50 mg/dl) at baseline; this patient abnormality was corrected in all cases after successful treatment. At baseline, the age-adjusted correlation between phosphate levels and state-anxiety was -0.66 (P < 0.001) among all 26 participants and -0.51 (P = 0.05) among the 16 panic disorder patients. CONCLUSIONS: Measurement of phosphate levels could be easily introduced into clinical practice as a possible marker for chronic hyperventilation in panic disorder, although further investigations with larger sample sizes are necessary to characterize panic disorder patients with low versus normal phosphate levels.

Weight gain and increase of body mass index among children and adolescents treated with antipsychotics: a critical review.

We performed an updated review of the available literature on weight gain and increase of body mass index (BMI) among children and adolescents treated with antipsychotic medications. A PubMed search was conducted specifying the following MeSH terms: (antipsychotic agents) hedged with (weight gain) or (body mass index). We selected 127 reports, including 71 intervention trials, 42 observational studies and 14 literature reviews. Second-generation antipsychotics (SGAs), in comparison with first-generation antipsychotics, are associated with a greater risk for antipsychotic-induced weight gain although this oversimplification should be clarified by distinguishing across different antipsychotic drugs. Among SGAs, olanzapine appears to cause the most significant weight gain, while ziprasidone seems to cause the least. Antipsychotic-induced BMI increase appears to remain regardless of the specific psychotropic co-treatment. Children and adolescents seem to be at a greater risk than adults for antipsychotic-induced weight gain; and the younger the child, the higher the risk. Genetic or environmental factors related to antipsychotic-induced weight gain among children and adolescents are mostly unknown, although certain genetic factors related to serotonin receptors or hormones such as leptin, adiponectin or melanocortin may be involved. Strategies to reduce this antipsychotic side effect include switching to another antipsychotic drug, lowering the dosage or initiating treatment with metformin or topiramate, as well as non-pharmacological interventions. Future research should avoid some methodological limitations such as not accounting for age- and sex-adjusted BMI (zBMI), small sample size, short period of treatment, great heterogeneity of diagnoses and confounding by indication.

Analysis of two language-related genes in autism: a case-control association study of FOXP2 and CNTNAP2.

Impairment of language abilities is a common feature in autistic individuals. Heterozygous mutations in the Forkhead Box P2 (FOXP2) gene lead to a severe spoken language disorder. Recently, several studies have pinpointed the involvement of common variants of the Contactin-Associated Protein-Like 2 (CNTNAP2) gene, whose transcription is regulated by the product of FOXP2, in several disorders characterized by language impairments such as autism, specific language impairment (SLI), and selective mutism (SM). In the present study, common variants of the FOXP2 and the CNTNAP2 genes were analyzed through a case-control association study in 322 Spanish autistic patients and 524 controls. The results of this study suggest that common variants of FOXP2 are unlikely to contribute to autism susceptibility, in agreement with previous findings. Furthermore, we failed to replicate in our sample a previous association finding of two single nucleotide polymorphisms (rs2710102 and rs7794745) in the CNTNAP2 gene with autism. No evidence for the association of these genes with language traits was observed in our analysis.

[Brief Suicide Questionnaire. Inter-rater reliability]. / Protocolo breve de evaluación del suicidio: fiabilidad interexaminadores.

INTRODUCTION: Inter-rater agreement is a crucial aspect in the planning and performance of a clinical trial in which the main assessment tool is the clinical interview. The main objectives of this study are to study the inter-rater agreement of a tool for the assessment of suicidal behavior (Brief Suicide Questionnaire) and to examine whether the inter-examiner agreement when multiple ratings are made on a single subject is an efficient method to assess the reliability of an instrument. METHOD: In the context of designing a multicenter clinical trial, 32 psychiatrists assessed a videotaped clinical interview of a patient with suicidal behavior. In order to identify those items in which a greater level of discordance existed and detect the examiners whose ratings differed significantly from the average ratings, we used the DOMENIC method (Detecion of Multiple Examiners Not in Consensus). RESULTS: Inter-rater agreement was between poor (<70%) to excelent (90-100%. Inter-rater agreement in Brugha's list of threatening experiences ranged from 75.5 and 100%; in the Global Assessment of Functioning (GAF) Scale was 82.58%; in the Beck's Suicidal Intent Scale, ranged from 67.5 and 97%; in the Beck's Scale for Suicide Ideation, ranged from 63.5 and 100%; and in the Lethality Rating Scale was 88.39%. On the whole, the level of agreement among raters, both in general scores and in particular items, was appropriate. CONCLUSION: The proposed design allows the assessment of the inter-rater agreement in an efficient way (only in one session). In addition, regarding the Brief Suicide Questionnaire, inter-raters agreement was appropriate.