Association of Prolactin, Oxytocin, and Homocysteine With the Clinical and Cognitive Features of a First Episode of Psychosis Over a 1-Year Follow-Up.

BACKGROUND: The clinical debut of schizophrenia is frequently a first episode of psychosis (FEP). As such, there is considerable interest in identifying associations between biological markers and clinical or cognitive characteristics that help predict the progression and outcome of FEP patients. Previous studies showed that high prolactin, low oxytocin, and high homocysteine are factors associated with FEP 6 months after diagnosis, at which point plasma levels were correlated with some clinical and cognitive characteristics. METHODS: We reexamined 75 patients at 12 months after diagnosis to measure the evolution of these molecules and assess their association with clinical features. RESULTS: At follow-up, FEP patients had lower prolactin levels than at baseline, and patients treated with risperidone or paliperidone had higher prolactin levels than patients who received other antipsychotic agents. By contrast, no changes in oxytocin and homocysteine plasma levels were observed between the baseline and follow-up. In terms of clinical features, we found that plasma prolactin and homocysteine levels were correlated with the severity of the psychotic symptoms in male FEP patients, suggesting that they might be factors associated with psychotic symptomatology but only in men. Together with oxytocin, these molecules may also be related to sustained attention, verbal ability, and working memory cognitive domains in FEP patients. CONCLUSION: This study suggests that focusing on prolactin, oxytocin, and homocysteine at a FEP may help select adequate pharmacological treatments and develop new tools to improve the outcome of these patients, where sex should also be borne in mind.

The polygenic basis of relapse after a first episode of schizophrenia.

Little is known about genetic predisposition to relapse. Previous studies have linked cognitive and psychopathological (mainly schizophrenia and bipolar disorder) polygenic risk scores (PRS) with clinical manifestations of the disease. This study aims to explore the potential role of PRS from major mental disorders and cognition on schizophrenia relapse. 114 patients recruited in the 2EPs Project were included (56 patients who had not experienced relapse after 3 years of enrollment and 58 patients who relapsed during the 3-year follow-up). PRS for schizophrenia (PRS-SZ), bipolar disorder (PRS-BD), education attainment (PRS-EA) and cognitive performance (PRS-CP) were used to assess the genetic risk of schizophrenia relapse.Patients with higher PRS-EA, showed both a lower risk (OR=0.29, 95% CI [0.11-0.73]) and a later onset of relapse (30.96± 1.74 vs. 23.12± 1.14 months, p=0.007. Our study provides evidence that the genetic burden of neurocognitive function is a potentially predictors of relapse that could be incorporated into future risk prediction models. Moreover, appropriate treatments for cognitive symptoms appear to be important for improving the long-term clinical outcome of relapse.

Affective temperaments and sexual functioning in euthymic patients with bipolar disorder.

Sexual functioning in bipolar disorder (BD) is dependent on multiple clinical and demographic determinants that can eventually lead to sexual dysfunction. However, the contribution of affective temperaments remains unstudied in this population. In this cross-sectional multicentric work, we studied the impact of temperament traits on sexual functioning in 100 euthymic BD outpatients treated only with mood stabilizers with or without benzodiazepines. Temperament was evaluated using the Temperament Evaluation of Memphis, Pisa, Paris, and San Diego - Autoquestionnaire (TEMPS-A) and sexual functioning with the Changes on Sexual Functioning Questionnaire (CSFQ-14). The effect of temperament on sexual functioning was analyzed using Bayesian ordinal regression models, which included age, gender, BD type, dominant polarity, metabolic syndrome, marital status, and affective symptomatology. Our results showed that hyperthymic traits predicted a significantly higher CSFQ-14 score for global sexual functioning (OR = 1.222; 95% CI [1.073, 1.431]), desire (OR = 1.164; 95% CI [1.025, 1.357]), arousal (OR = 1.278; 95% CI: [1.083, 1.551]), and orgasm (OR = 1.182; 95% CI [1.037, 1.365]). We did not find a significant contribution for other types of temperaments. Better sexual functioning was also associated with a better quality of life. Our findings highlight the importance of temperament traits in sexual functioning in euthymic BD, which may have implications in sexual dysfunction prevention.

Examining the independent and joint effects of genomic and exposomic liabilities for schizophrenia across the psychosis spectrum.

AIMS: Psychosis spectrum disorder has a complex pathoetiology characterised by interacting environmental and genetic vulnerabilities. The present study aims to investigate the role of gene-environment interaction using aggregate scores of genetic (polygenic risk score for schizophrenia (PRS-SCZ)) and environment liability for schizophrenia (exposome score for schizophrenia (ES-SCZ)) across the psychosis continuum. METHODS: The sample consisted of 1699 patients, 1753 unaffected siblings, and 1542 healthy comparison participants. The Structured Interview for Schizotypy-Revised (SIS-R) was administered to analyse scores of total, positive, and negative schizotypy in siblings and healthy comparison participants. The PRS-SCZ was trained using the Psychiatric Genomics Consortiums results and the ES-SCZ was calculated guided by the approach validated in a previous report in the current data set. Regression models were applied to test the independent and joint effects of PRS-SCZ and ES-SCZ (adjusted for age, sex, and ancestry using 10 principal components). RESULTS: Both genetic and environmental vulnerability were associated with case-control status. Furthermore, there was evidence for additive interaction between binary modes of PRS-SCZ and ES-SCZ (above 75% of the control distribution) increasing the odds for schizophrenia spectrum diagnosis (relative excess risk due to interaction = 6.79, [95% confidential interval (CI) 3.32, 10.26], p < 0.001). Sensitivity analyses using continuous PRS-SCZ and ES-SCZ confirmed gene-environment interaction (relative excess risk due to interaction = 1.80 [95% CI 1.01, 3.32], p = 0.004). In siblings and healthy comparison participants, PRS-SCZ and ES-SCZ were associated with all SIS-R dimensions and evidence was found for an interaction between PRS-SCZ and ES-SCZ on the total (B = 0.006 [95% CI 0.003, 0.009], p < 0.001), positive (B = 0.006 [95% CI, 0.002, 0.009], p = 0.002), and negative (B = 0.006, [95% CI 0.004, 0.009], p < 0.001) schizotypy dimensions. CONCLUSIONS: The interplay between exposome load and schizophrenia genetic liability contributing to psychosis across the spectrum of expression provide further empirical support to the notion of aetiological continuity underlying an extended psychosis phenotype.

Association of cannabinoid receptor genes (CNR1 and CNR2) polymorphisms and panic disorder.

Background and objectives: Panic disorder (PD) is an anxiety disorder characterized by recurrent and unexpected panic attacks along with sudden onset of apprehension, fear or terror. The endocannabinoid system (ECS) has a role in stress recovery, regulating anxiety. The aim of this study was to analyze potential genetic alterations in key ECS targets in patients suffering from panic disorders.Design and methods: We analyzed single nucleotide polymorphisms (SNPs) of the cannabinoid receptors (CNR1; CNR2) and the endocannabinoid hydrolytic enzyme fatty acid amide hydrolase (FAAH) genes in 164 Spanish PD patients and 320 matched controls.Results: No significant differences were observed in the SNPs of the CNR2 and FAAH genes tested. However, when analyzing genotype-by-sex interaction at A592G (rs2501431) and C315T (rs2501432) in the CNR2 gene, the presence of the G-allele in males was associated with a protective haplotype. Genotyping analysis revealed that variants in CNR1 confer vulnerability to PD, with a significantly increased risk associated with the G-allele (rs12720071) and C-allele (rs806368). This finding was consistent when analyzing genotype-by-sex interaction, where females presented a greater PD risk.Conclusions: Polymorphisms at the CNR1 gene may be a risk factor for PD contributing to sex-specific dysfunction in females.

Spanish validation of the Barcelona TEMPS-A questionnaire in patients with bipolar disorder and general population.

BACKGROUND: The Temperament Evaluation of the Memphis, Pisa, Paris, and San Diego (TEMPS-A) is a self-administered questionnaire intended to assess five affective temperaments: depressive, cyclothymic, hyperthymic, irritable and anxious. Our objective was to examine the psychometric properties of the TEMPS-A using a sample comprised by patients with bipolar disorder (BD) and healthy controls (HC) and to determine cut-off scores for each temperament. METHODS: Five hundred and ninety-eight individuals (327 BD and 271 HC) completed the TEMPS-A. Cronbach's alpha was used to examine internal consistency reliability. Test-retest reliability and association between different temperamental scales were assessed using Spearman correlation. To confirm factor structure a confirmatory factor analysis (CFA) was carried out. Cut-off scores indicating the presence of dominant temperament were also calculated. RESULTS: Internal consistency was optimal for all temperament subscales (α: 0.682- 0.893). The questionnaire demonstrated good test-retest reliability (ρ: 0.594-0.754). The strongest positive associations were found between cyclothymic and anxious and between depressive and anxious temperaments. Hyperthymic and depressive as well as hyperthymic and anxious temperaments showed a strong negative correlation. LIMITATIONS: The HC sample was not matched with the BD group. There were some sociodemographic and clinical differences between groups that may impact on the obtained results. A portion of patients with BD was recruited from tertiary centers. CONCLUSIONS: The Spanish version of the Barcelona TEMPS-A questionnaire presents a good internal consistency and their results are stable in clinical population. The performance of the Barcelona TEMPS-A is as good as the original scale.

Smoking does not impact social and non-social cognition in patients with first episode psychosis.

BACKGROUND: Many studies having shown significant improvements in non-social and social cognitive performance in smoking FEP patients compared to non-smoking FEP patients. The findings are controversial. This study analyzed the effects of tobacco use on non-social and social cognitive function in a large group of FEP patients and a matched healthy control group. METHODS: A sample of 335 patients with FEP and 253 healthy controls was divided into four subgroups: control tobacco users (CTU), control non-tobacco users (CNTU), patient tobacco users (PTU) and patient non-tobacco users (PNTU). Demographic variables, tobacco use variables (presence or absence, frequency and duration of tobacco use), neurocognitive (non-social) performance and social cognition were assessed. RESULTS: Comparison of 4 subgroups in non-social cognitive function revealed significant differences after controlling for covariables in executive functions (F=13.45; p≤0.001) and working memory domains (F=4.30; p=0.005). CTU and CNTU subgroups scored higher in all the domains compared to the PTU and the PNTU subgroups respectively. Social cognitive function was also significantly different within the four subgroups, with control subgroups showing better social cognition than patient subgroups. Significant differences in the executive functions domain were observed when comparing PTU and CTU groups (F=19.60; p≤0.001). No significant differences were revealed in the comparison between the patient groups. CONCLUSIONS: This large study suggests that tobacco use in FEP patients is not related to better non-social or social cognitive performance.

Impact of childhood trauma on cognitive profile in bipolar disorder.

OBJECTIVES: Bipolar Disorder (BD) is associated with cognitive impairment even during remission periods. Nonetheless, this impairment seems to adjust to different profiles of severity. Our aim was to examine the potential impact of childhood trauma (CT) on cognitive performance and, more specifically, on neurocognitive profile membership. METHODS: Using a data-driven strategy, 113 euthymic bipolar patients were grouped according to their cognitive performance using a hierarchical clustering technique. Patients from the three resulting clusters, the so-called "low", "average", and "high performance" groups, were then compared in terms of main sociodemographic, clinical and functioning variables, including CT measures. One-way ANOVA, a chi-square test and partial correlations were used for this purpose, as appropriate. A multinomial logistic regression model was used to determine which variables contributed to neurocognitive clustering membership. RESULTS: Patients from the three neurocognitive clusters differed in terms of sociodemographic, clinical, functioning and CT variables. Scores on the Childhood Trauma Questionnaire (CTQ), especially on the physical negligence subscale, were also associated with a poor cognitive performance. The multinomial regression model indicated that CTQ total scores and the estimated intelligence quotient (IQ) significantly contributed to differentiation among the three neurocognitive groups. CONCLUSIONS: Our results confirmed that CT significantly impacts on cognitive performance during adulthood in BD. The data obtained suggest that a history of CT could act as a liability marker for cognitive impairment. A higher estimated IQ may act as a protective factor against cognitive decline in this group of patients.

Suicide, unemployment, and economic recession in Spain. / Suicidio, desempleo y recesión económica en España.

INTRODUCTION: The aim of the present work is to determine the association between unemployment and suicide, and to investigate whether this association is affected by changes in the economic cycle or other variables such as age and sex. METHODS: A time-trend analysis was conducted to study changes in the number of suicides between 1999 and 2013 in Spain. Pearson's correlation coefficients and regression models were used to find the association between unemployment and suicide. RESULTS: A significant positive association was found between unemployment and suicide in the pre-crisis period in men. In that period (1999-2007), each 1% annual increase in unemployment was associated with a 6.90% increase in the annual variation of suicide in the total population, and with a 9.04% increase in the annual variation of suicide in working age men. CONCLUSIONS: The correlation between unemployment and suicide is significant in periods of economic stability, but has weakened during the recent financial crisis. Unemployment and suicide have a complex relationship modulated by age, sex and economic cycle.

Do patients with bipolar disorder and subsyndromal symptoms benefit from functional remediation? A 12-month follow-up study.

We analyzed the efficacy of functional remediation, in a sample of patients with bipolar disorder who presented with subsyndromal symptoms. From a total sample of 239 patients with bipolar I and II disorder, according to DSM-IV-TR diagnostic criteria, entering a randomized clinical trial, those patients who presented with subsyndromal symptoms were selected based on a method already described by Berk and colleagues was applied. It consists of using the Clinical Global Impression-Bipolar version (CGI-BP) to establish the scores of the Hamilton Depression Rating Scale (HAM-D) and of the Young Mania Rating Scale (YMRS) that correspond with 1 in the CGI-BP. Functional outcome and mood symptoms were assessed at 6 and at 12-month follow-up. A total of 99 patients were selected for this post-hoc analysis, allocated as follows: functional remediation (n=33); psychoeducation (n=37) and treatment as usual (TAU,n=29). The repeated-measures analyses at 12-month follow-up revealed a significant group x time interaction in favour of the patients who received functional remediation when compared to psychoeducation and TAU (F=2.93; p=0.02) at improving psychosocial functioning. Finally, mood symptoms did not significantly change in any of the three groups at any time of follow-up, as shown by the non-significant group x time interaction effect in HAM-D scores (F=1.57; p=0.18) and YMRS scores (F=1.51; p=0.20). Bipolar patients with subsyndromal symptoms improve their functional outcome when exposed to functional remediation regardless of the persistence of mood symptomatology.

Tobacco and cognitive performance in schizophrenia patients: the design of the COGNICO study. / Tabaco y rendimiento cognitivo en pacientes con esquizofrenia: diseño del estudio COGNICO.

People with schizophrenia constitute a substantial part of the people who still smoke. Regarding cognitive performance, the self-medication hypothesis states that patients smoke to improve their cognitive deficits based on the stimulating effects of nicotine. The aim of this paper is to describe in detail the methodology used in the COGNICO study. A quasi-experimental, observational, prospective, multicenter study with follow-ups over 18 months was conducted in three cities in northern Spain (Oviedo, Ourense and Santiago de Compostela). A total of 81 outpatient smokers with schizophrenia were recruited with a mean age 43.35 years (SD = 8.83), 72.8% of them male. They were assigned to 3 groups: a) control group (smokers); b) patients who quit smoking using nicotine patches; c) patients who quit smoking with Varenicline. The MATRICS neuropsychological battery was applied as a primary measure. In addition, a comprehensive assessment of patients was performed, including the number of cigarettes per day, physical and psychological dependence on nicotine and CO expired. Clinical evaluation (PANSS, HDRS, CGI, C-SSRS), anthropometric measurements and vital signs assessment was also performed. The aim is to identify the relationship between the pattern of tobacco use and cognitive performance by comparing scores on the neuropsychological battery MATRICS during the follow-up periods (3, 6, 12 and 18months). The importance of this study lies in addressing a topical issue often ignored by clinicians: the unacceptably high rates of tobacco use in patients with severe mental disorders.

Las personas con esquizofrenia constituyen una parte sustancial de las personas que todavía fuman. La hipótesis de la automedicación en relación al rendimiento cognitivo mantiene que los pacientes fuman para mejorar su déficit cognitivo basándose en los efectos estimulantes de la nicotina. El objetivo de este artículo es describir la metodología del estudio COGNICO. Estudio cuasiexperimental, observacional, prospectivo, multicéntrico y  con seguimiento a 3, 6, 12 y 18 meses. Fue llevado a cabo en tres ciudades del norte de España (Oviedo, Ourense y Santiago de Compostela). Se reclutaron 81pacientes con esquizofrenia fumadores (edad media de 43,35 años (DT=8,83). 72,8% varones). Se asignaron a 3 grupos: a) control: pacientes fumadores; b) pacientes que dejan de fumar mediante parches de nicotina; c) pacientes que dejan de fumar mediante vareniclina. Como medida primaria se aplicó la batería neuropsicológica MATRICS. Además, se llevó a cabo una evaluación comprehensiva de los pacientes, que incluía  el número de cigarrillos por día, la dependencia física y psicológica a la nicotina y el CO expirado. También se realizó una evaluación clínica general (PANSS, HDRS, ICG, C-SSRS) así como un seguimiento de las medidas antropométricas y los signos vitales. Se pretende  identificar la relación entre el patrón de consumo de tabaco y el rendimiento cognitivo mediante la comparación de las puntuaciones en la batería neuropsicológica MATRICS durante los períodos de seguimiento.

Psychometric properties of a Spanish-version of the Schizophrenia Objective Functioning Instrument (Sp-SOFI).

The Schizophrenia Objective Functioning Instrument (SOFI) is an interviewer-administered scale designed to objectively assess the actual level of patient functioning and to measure community functioning related to cognitive impairment and psychopathology. The aim was to examine the psychometric properties of the Spanish version of the SOFI (Sp-SOFI) in a sample of 155 Spanish outpatients with schizophrenia disorder. The instruments applied were Sp-SOFI, Positive and Negative Syndrome Scale (PANSS), Clinical Global Impression-Schizophrenia Scale (CGI-SCH), Personal and Social Performance Scale (PSP), and Global Assessment of Functioning (GAF). The discrimination indexes of the Sp-SOFI items range from .21 to .77. Exploratory factor analysis showed an essentially one-dimensional structure. Cronbach's alpha was .93. Test-retest reliability for the Sp-SOFI total score was .87 (p < .001). The canonical correlation between SP-SOFI domains and PSP dimensions was .83. The multiple correlation coefficient between Sp-SOFI domains and GAF score was .84. Sp-SOFI scores were significantly different between high and low scores on the PANSS scales (p < .001). Sp-SOFI measures discriminated among patients with doubtful, mild, moderate, and severe schizophrenia disorder according to CGI-SCH scales (p < .001). New evidence about the validity of the SOFI was provided. The Sp-SOFI is a reliable and valid tool for using in clinical practice.

El Instrumento de Funcionamiento Objetivo para la Esquizofrenia (SOFI) es una entrevista para evaluar el nivel de funcionamiento comunitario en relación con el daño cognitivo y los síntomas psicopatológicos. El objetivo del estudio consistió en examinar las propiedades psicométricas de la versión española de la SOFI (Sp-SOFI) en una muestra de 155 pacientes ambulatorios con esquizofrenia. Los índices de discriminación de la Sp-SOFI oscilaron entre 0,21 y 0,77. El análisis factorial exploratorio mostró una estructura esencialmente unidimensional. El alfa de Cronbach fue 0,93. El coeficiente de fiabilidad test-retest fue 0,87 (p < 0,001). La correlación canónica entre la Sp-SOFI y la Escala de Funcionamiento Personal y Social (PSP) fue 0,83. El coeficiente de correlación múltiple entre la Sp-SOFI y la Escala de Evaluación de la Actividad Global (EEAG) fue 0,44. Las puntuaciones en la Sp-SOFI fueron significativamente diferentes entre los pacientes con puntuaciones altas y bajas en la Escala del Síndrome Positivo y Negativo (PANSS) (p < 0,001). La Sp-SOFI discriminó entre pacientes con trastorno de esquizofrenia dudoso, leve, moderado y grave de acuerdo con la Escala de Impresión Clínica Global de Esquizofrenia (CGI-SCH) (p < 0,001). La Sp-SOFI es un instrumento fiable y válido para la práctica clínica.

Exploring Genetic Variability at PI, GSK3, HPA, and Glutamatergic Pathways in Lithium Response: Association With IMPA2, INPP1, and GSK3B Genes.

Lithium is considered the first-line treatment in bipolar disorder, although response could range from an excellent response to a complete lack of response. Response to lithium is a complex phenotype in which different factors, part of them genetics, are involved. In this sense, the aim of this study was to investigate the potential association of genetic variability at genes related to phosphoinositide, glycogen synthetase kinase-3 (GSK3), hypothalamic-pituitary-adrenal, and glutamatergic pathways with lithium response. A sample of 131 bipolar patients (99 type I, 32 type II) were grouped and compared according to their level of response: excellent responders (ER), partial responders (PR), and nonresponders (NR). Genotype and allele distributions of the rs669838 (IMPA2), rs909270 (INNP1), rs11921360 (GSK3B), and rs28522620 (GRIK2) polymorphisms significantly differed between ER, PR, and NR. When we compared the ER versus PR+NR, the logistic regression showed significant association for rs669838-C (IMPA2; P = 0.021), rs909270-G (INPP1; P = 0.009), and rs11921360-A (GSK3B; P = 0.004) with lithium nonresponse. Haplotype analysis showed significant association for the haplotypes rs3791809-rs4853694-rs909270 (INPP1) and rs1732170-rs11921360-rs334558 (GSK3B) and lithium response. Our study is in line with previous studies reporting association between genetic variability at these genes and lithium response, pointing to an effect of IMPA2, INPP1, and GSK3B genes to lithium response in bipolar disorder patients. Further studies with larger samples are warranted to assess the strength of the reported associations.

Functional remediation for patients with bipolar II disorder: improvement of functioning and subsyndromal symptoms.

Recently, Functional Remediation (FR) has proven to be effective in improving the functional outcome of euthymic bipolar patients. The aim of this study was to test the efficacy of the FR program in a subsample of euthymic bipolar II patients (BPII). A post-hoc analyses were undertaken using data of 53 BPII outpatients who had participated in a multicenter, rater-blind, randomized, controlled trial exploring the efficacy of FR (n=17) as compared with a Psychoeducation group (PSY) (n=19) and a treatment as usual control group (TAU n=17). The primary outcome variable was the functional improvement defined as the mean change in the Functioning Assessment Short Test (FAST) from baseline to endpoint after the intervention. Regarding the treatment effect, data reveal a significant functional improvement from baseline to endpoint, suggestive for an interaction between program pertinence and time (pre-post). Nevertheless, Tukey׳s post-hoc test only revealed a trend in favor of a better outcome for FR when compared to the other two groups. We also found an interaction between program pertinence and time when analysing the subdepressive symptoms, with BPII patients in FR showing a significant reduction when compared to the PSY group. Our results suggest that the FR appears to be effective in improving the overall functional outcome in BPII, as well as in reducing subdepressive symptoms.

Association between GSK3ß gene and increased impulsivity in bipolar disorder.

Bipolar patients present increased levels of impulsivity even during remission periods. It is known that this dimensional trait negatively impacts on the course of illness and worsens their prognosis and outcome. Evidence from both basic and clinical researches supports that Lithium (Li) may decrease impulsivity. Owing to the fact that Li inhibits both glycogen synthetase kinase-3 (GSK3) isoenzimes, our aim was to analyze the potential impact of genetic variants located at the GSK3 α and ß genes on impulsivity levels in a bipolar sample. Our sample consisted of 199 unrelated Caucasian bipolar outpatients who were recruited from the Bipolar Disorder Unit of the Hospital Clinic of Barcelona and from primary care settings from Oviedo. Four polymorphisms at the GSK3 α and ß genes were genotyped in order to analyze the impact of genetic variability on impulsivity as measured by the BIS-11 scale. Single SNP analysis showed that patients carrying T and G alleles at the rs1732170-GSK3ß and the rs334558-GSK3ß, respectively, presented increased levels of attentional impulsivity compared to non-carriers. These results were also confirmed by haplotype analysis. Our results suggest that genetic variability at GSK3ß gene is associated to increased impulsivity in bipolar patients.

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.

The incidence of hospital-treated attempted suicide in Oviedo, Spain.

BACKGROUND: The incidence of hospital-treated attempted suicide has not been well established in Spain. AIMS: To determine the incidence of suicide attempters presenting to a hospital in Oviedo, Spain, to describe the nature of the suicidal behavior, and to identify sociodemographic subgroups of the population with high rates. METHODS: All admitted to the Hospital Universitario Central de Asturias, Oviedo, during the period 1 May 2008 to 30 April 2009 were examined and those meeting the internationally-recognized case definition were identified. RESULTS: A total of 308 suicide attempt presentations (39% male, 61% female) were made by 279 individuals. Almost 90% of the suicide attempts involved a drug overdose. The age-adjusted total, male, and female attempted suicide rates were 83, 66, and 99 per 100,000, respectively. The highest rate was among 35-44-year-olds for men and women (141.1 and 191.8 per 100,000, respectively). Incidence rates varied widely by sociodemographic characteristics with especially high rates among separated/divorced men (2.4%) and women (1.1%). CONCLUSIONS: The reported incidence of hospital-treated attempted suicide is below average in the European context but higher than that reported by previous Spanish studies. Persons separated or divorced constitute a high-risk group.

A 25-year follow-up of patients admitted to methadone treatment for the first time: mortality and gender differences.

INTRODUCTION: We conducted a follow-up study to evaluate the outcome of a heroin-dependent population 25 years after their first enrollment in methadone maintenance treatment (MMT). We assessed mortality in the sample plus actual drug use, treatment, and medical factors associated with drug dependence, focusing on possible gender differences. METHODS: Prospective follow-up study of 214 heroin-dependent patients consecutively admitted for MMT between 1980 and 1984 in the Asturias Public Health Service. The standardized mortality ratio (SMR) and 95% confidence interval (CI) were calculated. An ad-hoc protocol on drug misuse and treatment, drug-related morbidity and Clinical Global Impression (CGI) scores were assessed in the survivors' sample. RESULTS: Information was received on 159 subjects, 106 of whom were deceased. Men accounted for 76.2% of the study cohort. Over the 25-year follow-up period, the SMR was 22.51 (95% CI=22.37-22.64). In the survivors sample, 39.6% were still enrolled in MMT; human immunodeficiency virus (HIV) was diagnosed in 47.2% and hepatitis B/C in 81.1%; current heroin use was reported by 22.6%. There were no gender differences in mortality or HIV and hepatitis B/C status. None of the female survivors were using heroin at the 25-year follow-up compared with 31.1% of males. CONCLUSIONS: This study confirms the high mortality of heroin addicts even after enrollment in MMT. Severity of the addiction in terms of mortality was similar in both genders. Women who survived the 25-year follow-up were more likely to have stopped using heroin than men.

Genetic polymorphisms in the dopamine-2 receptor (DRD2), dopamine-3 receptor (DRD3), and dopamine transporter (SLC6A3) genes in schizophrenia: Data from an association study.

OBJECTIVE: To investigate the association between dopaminergic polymorphisms [DRD2 -141C Ins/Del, DRD3 Ser9Gly, and SLC6A3 VNTR] and schizophrenia. METHODS: Two hundred and eighty-eight outpatients with schizophrenia (DSM-IV criteria) [mean age (SD)=36.4 (12.4), 60.1% males] and 421 unrelated healthy controls [mean age (SD)=40.6 (11.3), 51.3% males] from a homogeneous Spanish Caucasian population were genotyped using standard methods. RESULTS: There was a significant difference in genotype distribution for the DRD2 -141C Ins/Del polymorphism [(chi(2) (2)=12.35, corrected p=0.012]. The -141C Del allele was more common in patients than in controls [0.19 vs. 0.13; chi(2) (1)=9.14, corrected p=0.018, OR (95% CI)=1.57 (1.17-2.10)]. Genotype and allele distributions for DRD3 Ser9Gly and SLC6A3 VNTR polymorphisms were similar in both groups. However, there was tentative evidence of an interaction effect between DRD3 Ser9Gly and SLC6A3 VNTR [Wald=9.56 (4), p=0.049]. Compared to the SLC6A3 10/10 genotype category, the risk of schizophrenia was halved among those with 9/10 [OR=0.51 (95% CI=0.30-0.89), p=0.017]. This protective effect was only present in combination with DRD3 Ser/Ser genotype because of the significant interaction between 9/10 and both Ser/Gly [OR=2.45 (95% CI=1.16-5.17), p=0.019] and Gly/Gly [OR=3.80 (95% CI=1.24-11.63), p=0.019]. CONCLUSIONS: This study provides evidence that a genetic variant in the DRD2 gene and possible interaction between DRD3 and SLC6A3 genes are associated with schizophrenia. These findings warrant examination in replication studies.