Association between neutrophil to lymphocyte ratio and inflammatory biomarkers in patients with a first episode of psychosis.

Neutrophil to lymphocyte ratio (NLR) has been proposed as an emerging marker of the immune system alterations in psychotic disorders. However, it is not entirely clear whether NLR elevation is a characteristic of the psychotic disorder itself, which inflammatory pathways activation is detecting, or which possible confounding variables could alter its interpretation. We aimed to analyze the relationship of NLR values with a panel of inflammatory and oxidative/nitrosative stress biomarkers and main potential confounding factors in a well-characterized cohort of 97 patients with a first episode of psychosis (FEP) and 77 matched healthy controls (HC). In the FEP group, NLR values presented a moderate, positive correlation with the pro-inflammatory mediator Prostaglandin E2 levels (r = 0.36, p < 0.001) and a small but significant, positive correlation with cannabis use (r = 0.25, p = 0.017). After controlling for cannabis use, the association between NLR and PGE2 remained significant (beta = 0.31, p = 0.012). In the HC group, NLR values negatively correlated with body mass index (BMI, r = -0.24, p = 0.035) and positively correlated with tobacco use (r = 0.25, p = 0.031). These findings support a relationship between the elevation of NLR values and an elevated expression of proinflammatory pathways related to stress response in patients with a FEP. In addition, our study highlights the importance of considering variables such as cannabis or tobacco consumption, and BMI when interpreting the results of studies aimed to establish a clinical use of NLR. These considerations may help future research to use NLR as a reliable biomarker to determine immune system status in this population.

Platelet and white blood-cell-based ratios: Differential inflammatory markers of severe mental disorders?

INTRODUCTION: Neutrophil/lymphocyte (NLR), monocyte/lymphocyte (MLR), and platelet/lymphocyte (PLR) ratios, and systemic inflammatory index (SII) represent peripheral markers of inflammation associated with different severe mental disorders. MATERIAL AND METHODS: In this study, these parameters were analyzed in a sample of 622 participants [197 patients with major depressive disorder (MDD), 154 with bipolar disorder (BD), 176 with schizophrenia (SCH), and 95 healthy controls (HC)]. Sociodemographic and clinical data of patients were recorded. RESULTS: Differences in age and sex were detected among groups (p<0.001), with SCH patients being younger and MDD patients being older. After stratifying by sex, these ratios were compared using the nonparametric ANCOVA (Quade's test) using age as a covariate. In males, no significant statistical differences were found between groups. However, differences were observed in MLR in the subgroup of females [MDD: 0.23 (SD=0.09); BD: 0.23 (SD=0.11); SCH: 0.24 (SD=0.11); HC: 0.29 (SD=0.13); F=5.376, p=0.001]. Post hoc testing revealed that there are MLR differences between HC versus MDD and between HC versus BD, with higher values in HC versus the other two groups. On the other hand, no differences were found in either males or females for any of the studied ratios, among the three diagnostic groups. CONCLUSIONS: MLR is reduced in MDD and BD patients versus HC, but exclusively in the female group. However, based on the analyzed indices, it is not possible to differentiate among the three diagnostic groups of patients. As a limitation of this study, note that the effects of psychopharmacological treatments and smoking have not been controlled for.

Clinical practice guideline on pharmacological and psychological management of adult patients with schizophrenia spectrum disorders and a comorbid substance use. / Guía de práctica clínica para el tratamiento farmacológico y psicológico de los pacientes adultos con un trastorno del espectro esquizofrénico y un diagnóstico comórbido de trastorno por uso de sustancias.

Although correct diagnosis and management of patients with schizophrenia and a comorbid substance use disorder (SUD) would determine a decrease in morbidity and mortality in these patients, development of efficient therapeutic strategies is still pending. We present recommendations on the pharmacological and psychological management of these patients following the 'PICO' structure (Patient-Intervention-Comparison-Outcomes). Evaluation of the quality of studies and summary of the evidence for each question was performed following the recommendations of the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) working group. Our results suggest: 1) In patients with schizophrenia and cannabis use disorder, it is not possible to recommend one antipsychotic drug over another (between olanzapine, risperidone or haloperidol) for improving psychotic symptoms, reducing cannabis use, or improving pragmatic variables (weak recommendation). Clozapine cannot be recommended to reduce cannabis use (weak recommendation). 2) In patients with schizophrenia and cocaine use disorder we recommend haloperidol over olanzapine to reduce craving (moderate recommendation), and olanzapine over haloperidol to improve motor side effects in these patients (moderate recommendation). 3) In patients with schizophrenia and alcohol use disorder while naltrexone is recommended to reduce alcohol use (in terms of reducing alcohol craving) (weak recommendation), there is insufficient evidence to make any recommendation on the use of adjuvant acamprosate (weak recommendation). 4) In patients with schizophrenia and nicotine use disorder, adjuvant bupropion and varenicline are recommended for reducing nicotine use and nicotine abstinence (strong/moderate recommendation). 5) In patients with schizophrenia and polydrug use disorder, second-generation over first-generation antipsychotic drugs and olanzapine over other second-generation antipsychotics are recommended to improve psychotic symptoms (moderate/weak recommendation).

Aunque el correcto diagnóstico y manejo de los pacientes con esquizofrenia y un diagnóstico comórbido de trastorno por uso de sustancias (TUS) determinaría una disminución de la morbilidad y mortalidad en estos pacientes, el desarrollo de estrategias terapéuticas eficientes es todavía una asignatura pendiente. Presentamos recomendaciones sobre el manejo farmacológico y psicológico de estos pacientes siguiendo la estructura PICO (Paciente-Intervención-Comparación-Outcome/resultados). Realizamos una evaluación de la calidad de los estudios y un resumen de la evidencia para cada pregunta siguiendo las recomendaciones del grupo de trabajo GRADE («Grading of Recommendations, Assessment, Development and Evaluation¼). Nuestros resultados sugieren: 1) En pacientes con esquizofrenia y trastorno por consumo de cannabis, no es posible recomendar un fármaco antipsicótico sobre otro (entre olanzapina, risperidona o haloperidol) para mejorar los síntomas psicóticos, reducir el consumo de cannabis o mejorar las variables pragmáticas (recomendación débil). No se puede recomendar la clozapina para reducir el consumo de cannabis (recomendación débil). 2) En pacientes con esquizofrenia y trastorno por consumo de cocaína, recomendamos haloperidol sobre olanzapina para reducir el craving (recomendación moderada) y olanzapina sobre haloperidol para mejorar los efectos secundarios motores en estos pacientes (recomendación moderada). 3) En pacientes con esquizofrenia y trastorno por consumo de alcohol, mientras que se recomienda naltrexona para reducir el consumo de alcohol (en términos de reducción del craving de alcohol) (recomendación débil), no hay evidencia suficiente para hacer ninguna recomendación sobre el uso de acamprosato como adyuvante (recomendación débil). 4) En pacientes con esquizofrenia y trastorno por consumo de nicotina, se recomiendan bupropión y vareniclina adyuvantes para reducir el consumo y la abstinencia de nicotina (recomendación fuerte/moderada). 5) En pacientes con esquizofrenia y trastorno por policonsumo, se recomiendan antipsicóticos de segunda generación sobre los de primera generación y olanzapina sobre otros antipsicóticos de segunda generación para mejorar los síntomas psicóticos (recomendación moderada/débil).

Clinical practice guideline on pharmacological and psychological management of adult patients with depression and a comorbid substance use disorder. / Guía de práctica clínica para el tratamiento farmacológico y psicológico de los pacientes adultos con depresión y un diagnóstico comórbido de trastorno por uso de sustancias.

Co-occurrence of depression and a substance use disorder (SUD) in patients who present dual diagnoses has been long recognized as an important consideration in clinical practice. This review synthesizes the evidence of pharmacological and psychosocial interventions for comorbid depressive disorders and SUDs while providing clinical recommendations about the best interventions to address these patients. The best evidence from randomized controlled trials was used to evaluate treatment options. The strength of recommendations was described using the GRADE approach. Our results suggest that 1) In patients with depression and alcohol consumption, the administration of non-selective serotonin reuptake inhibitor (SSRI) antidepressants instead of SSRI is recommended for improvement of depressive symptoms (strong recommendation). Neither SSRI (strong recommendation) nor non-SSRI (weak recommendation) antidepressants are recommended for reduction in alcohol consumption. 2) In patients with depression and cannabis use, the use of venlafaxine is not recommended (weak recommendation). 3) In patients with depression and cocaine consumption, the use of SSRI antidepressants for improving depressive symptoms (weak recommendation) or to reduce cocaine use is not recommended (strong recommendation). The use of non-SSRI antidepressants is only recommended for improving depressive symptoms (strong recommendation). 4) The administration of bupropion to reduce nicotine consumption is not recommended (strong recommendation). 5) Regarding psychological treatment, in patients with depression and co-occurring alcohol disorder, both pharmacotherapy and cognitive behavioural therapy have positive effects on internalizing symptoms and in reducing alcohol consumption (weak recommendation). Our review suggests the need for more research in this area and for larger, multisite, randomized studies to provide more definite evidence.

La concurrencia de depresión y un trastorno por uso de sustancias (TUS) en pacientes que presentan patología dual ha sido reconocida desde hace mucho tiempo como una consideración importante en la práctica clínica. Esta revisión sintetiza la evidencia de intervenciones farmacológicas y psicosociales para trastornos comórbidos de depresión y uso de sustancias y además proporciona recomendaciones clínicas respecto de las mejores intervenciones para tratar a estos pacientes. Se utilizó la mejor evidencia de ensayos controlados aleatorizados para evaluar las opciones de tratamiento. La fuerza de las recomendaciones se describió mediante el enfoque GRADE. Nuestros resultados sugieren que: 1) en pacientes con depresión y consumo de alcohol, se recomienda la administración de antidepresivos inhibidores de la recaptación de serotonina (ISRS) no selectivos en lugar de los ISRS para mejorar los síntomas depresivos (recomendación fuerte). No se recomiendan antidepresivos ISRS (recomendación fuerte) ni antidepresivos no ISRS (recomendación débil) para reducir el consumo de alcohol; 2) en pacientes con depresión y consumo de cannabis, no se recomienda el uso de venlafaxina (recomendación débil); 3) en pacientes con depresión y consumo de cocaína, no se recomienda el uso de antidepresivos ISRS para mejorar los síntomas depresivos (recomendación débil) o para reducir el consumo de cocaína (recomendación fuerte). El uso de antidepresivos no ISRS solo se recomienda para mejorar los síntomas depresivos (recomendación fuerte); 4) no se recomienda la administración de bupropión para reducir el consumo de nicotina (recomendación fuerte), y 5) en cuanto al tratamiento psicológico, en pacientes con depresión y trastorno de alcohol concurrente, tanto la farmacoterapia como la terapia cognitivo-conductual tienen efectos positivos en la internalización de los síntomas y en la reducción del consumo de alcohol (recomendación débil). Nuestra revisión sugiere la necesidad de realizar más investigaciones en esta área y de estudios aleatorizados, multisitio y más grandes para proporcionar más evidencia definitiva.

Clinical practice guideline on pharmacological and psychological management of adult patients with bipolar disorder and comorbid substance use. / Guía de práctica clínica para el tratamiento farmacológico y psicológico de los pacientes adultos con trastorno bipolar y un diagnóstico comórbido de trastorno por uso de sustancias.

This review synthesizes the pharmacological and psychosocial interventions that have been conducted in comorbid bipolar disorder (BD) and substance use disorders (SUDs) while also providing clinical recommendations about which intervention elements are helpful for addressing substance use versus mood symptoms in patients with these co-occurring conditions. The best evidence from randomized controlled trials was used to evaluate treatment options. The strength of recommendations was described using the GRADE approach. Very few of the randomized trials performed so far have provided consistent evidence for the management of both mood symptoms and substance use in patients with a BD. No clinical trials are available for bipolar patients using cannabis. Some treatments have shown benefit for mood symptoms without benefits for alcohol or illicit substance use. Our results suggest that 1) we can (weakly) recommend the use of adjuvant valproate or naltrexone to improve symptoms of alcohol use disorder; 2) Lamotrigine add-on therapy seems to reduce cocaine-related symptoms and is therefore recommended (moderate strength); and 3) Varenicline is (weakly) recommended to improve nicotine abstinence. Integrated group therapy is the most-well validated and efficacious approach on substance use outcomes if substance use is targeted in an initial treatment phase.

Esta revisión resume las intervenciones farmacológicos y psicosociales que se han realizado en trastorno bipolar (TB) y un diagnóstico comórbido de trastorno por uso de sustancias (TUS) y además proporciona recomendaciones clínicas respecto de cuáles elementos de intervención son útiles para hacer frente a los síntomas del uso de sustancias versus los síntomas de estado de ánimo en pacientes con estas afecciones concurrentes. Se utilizó la mejor evidencia de ensayos controlados aleatorizados para evaluar las opciones de tratamiento. La fuerza de las recomendaciones se describió mediante el enfoque GRADE. Muy pocos de los ensayos aleatorizados realizados hasta la fecha han proporcionado evidencia consistente para el manejo tanto de los síntomas de estado de ánimo como del uso de sustancias en pacientes con TB. No hay disponibilidad de ensayos clínicos para pacientes con TB que utilizan el cannabis. Algunos tratamientos han mostrado beneficios para los síntomas de estado de ánimo sin beneficios para el uso de alcohol o sustancias ilícitas. Nuestros resultados sugieren que 1) podemos (débilmente) recomendar el uso de ácido valproico o naltrexona adyuvante para aliviar los síntomas del trastorno por consumo de alcohol; 2) el tratamiento complementario con lamotrigina parece reducir los síntomas relacionados con la cocaína y, por tanto, es recomendable (fuerza moderada); y 3) la vareniclina es recomendable (débilmente) para mejorar la abstinencia de la nicotina. La terapia grupal integrada es el enfoque con más validación y eficacia sobre los resultados en el uso de sustancias cuando este uso es abordado durante la fase inicial de tratamiento.

Clinical practice guideline on pharmacological and psychological management of adult patients with an anxiety disorder and comorbid substance use. / Guía de práctica clínica para el tratamiento farmacológico y psicológico de los pacientes adultos con un trastorno de ansiedad y un diagnóstico comórbido de trastorno por uso de sustancias.

This review synthesizes the pharmacological and psychosocial interventions that have been conducted in comorbid anxiety disorders and SUDs while also providing clinical recommendations about which intervention elements are helpful for addressing substance use versus anxiety symptoms in patients with these co-occurring conditions. The best evidence from randomized controlled trials was used to evaluate treatment options. The strength of recommendations was described using the GRADE approach. Clinical trials are only available for posttraumatic stress disorder (PTSD) and for social anxiety. Concerning the comorbid substance use, all the studies have included patients with alcohol use, none of them have dealt with cocaine, cannabis or nicotine use. Although some treatments have shown benefit for anxiety symptoms without benefits for alcohol or other substance use, only limited pharmacological approaches have been assayed (sertraline, desipramine, paroxetine, buspirone, naltrexone and disulfiram). Our results suggest that 1) we can (weakly) recommend the use of desipramine over paroxetine to alleviate symptoms of anxiety in patients with a PTSD and alcohol use; 2) In these patients, the use of naltrexone to reduce symptoms of anxiety is also recommended (weak strength); and 3) SSRI antidepressants vs placebo can be recommended to reduce alcohol use (weak recommendation). Our review highlights the need for more research in this area and for larger, multisite studies with generalizable samples to provide more definite guidance for clinical practice.

Esta revisión resume las intervenciones farmacológicos y psicosociales que han sido llevadas a cabo en trastornos de ansiedad con un diagnóstico comórbido de trastorno por uso de sustancias y además proporciona recomendaciones clínicas respecto de cuáles elementos de intervención son útiles para hacer frente a los síntomas del uso de sustancias y los síntomas de ansiedad en pacientes con estas afecciones concurrentes. Se utilizó la mejor evidencia de ensayos controlados aleatorizados para evaluar las opciones de tratamiento. La fuerza de las recomendaciones se describió mediante el enfoque GRADE. Hay ensayos clínicos disponibles únicamente para el trastorno por estrés postraumático (TEPT) y para el trastorno de ansiedad. En cuanto al diagnóstico comórbido de trastorno por uso de sustancias, todos los estudios han incluido pacientes con consumo de alcohol, ninguno de ellos ha abordado el consumo de cocaína, cannabis o nicotina. Aunque algunos tratamientos han mostrado beneficios para los síntomas de ansiedad sin beneficios para el consumo de alcohol u otras sustancias, solo se han ensayado enfoques farmacológicos limitados (sertralina, desipramina, paroxetina, buspirona, naltrexona y disulfiram). Nuestros resultados sugieren que 1) podemos (débilmente) recomendar el uso de desipramina sobre la paroxetina para aliviar los síntomas de ansiedad en pacientes con un TEPT y consumo de alcohol; 2) en estos pacientes, el uso de naltrexona para reducir los síntomas de ansiedad es también recomendable (fuerza débil); y 3) se pueden recomendar antidepresivos ISRS frente a placebo para reducir el consumo de alcohol (recomendación débil). Nuestra revisión pone de relieve la necesidad de realizar más investigaciones en esta área y de estudios más grandes, multisitio con muestras generalizables para proporcionar evidencia más definitiva para la práctica clínica.

Clinical practice guideline on pharmacological and psychological management of adult patients with attention deficit and hyperactivity disorder and comorbid substance use. / Guía de práctica clínica para el tratamiento farmacológico y psicológico de los pacientes adultos con trastorno por déficit de atención con hiperactividad y un diagnóstico comórbido de trastorno por uso de sustancias.

Substantial evidence has confirmed the high comorbidity between Attention-Deficit/Hyperactivity Disorder (ADHD) and a substance use disorder (SUD). This review synthesizes the pharmacological and psychosocial interventions conducted in ADHD and SUDs, and provides clinical recommendations using the GRADE approach. Our results suggest: 1) In patients with ADHD and alcohol use, atomoxetine is recommended to reduce ADHD symptoms (weak recommendation) and alcohol craving (weak recommendation). 2) In patients with ADHD and cannabis use disorder, atomoxetine is recommended to improve ADHD symptoms (weak recommendation), not to reduce cannabis use (weak recommendation). 3) In patients with ADHD and cocaine use disorder, methylphenidate is not recommended to improve ADHD symptoms or to reduce cocaine use (weak recommendation). 4) In patients with ADHD and comorbid nicotine use disorder, methylphenidate is recommended to improve ADHD symptoms (weak recommendation). Psychoestimulants, such as methylphenidate or lisdexamfetamine dimesylate, are not recommended to reduce nicotine use (weak recommendation). 5) Regarding patients with ADHD and any SUD, the use of psychostimulants is recommended to improve ADHD symptoms (weak recommendation), not to reduce substance use (weak recommendation) or to improve retention to treatment (strong recommendation). In these patients, the use of atomoxetine is recommended to improve ADHD symptoms (weak recommendation), not to decrease substance use (weak recommendation) or to improve retention to treatment (strong recommendation). Atomoxetine and psychostimulants appear to be safe in patients with any SUD (strong recommendation). Our review suggests the need for more research in this area and for larger, multisite, randomized studies to provide more definite and conclusive evidence.

La evidencia actual confirma la alta comorbilidad entre el trastorno por déficit de atención con hiperactividad (TDAH) y trastorno por uso de sustancias (TUS). Esta revisión resume las intervenciones farmacológicas y psicosociales que se han evaluado en pacientes con TDAH y TUS, y ofrece recomendaciones mediante el enfoque GRADE. Nuestros resultados sugieren: 1) En pacientes con TDAH y trastorno por uso de alcohol, la atomoxetina es recomendable para reducir los síntomas de TDAH (recomendación débil) y el craving de alcohol (recomendación débil). 2) En pacientes con TDAH y trastorno por uso de cannabis, la atomoxetina es recomendable para mejorar los síntomas de TDAH (recomendación débil), no para reducir el uso de cannabis (recomendación débil). 3) En pacientes con TDAH y trastorno por uso de cocaína, el metilfenidato no es recomendable para mejorar los síntomas de TDAH o para reducir el uso de cocaína (recomendación débil). 4) En pacientes con TDAH y trastorno por uso de nicotina, es recomendable el metilfenidato para mejorar los síntomas de TDAH (recomendación débil). Los psicoestimulantes, como metilfenidato o lisdexanfetamina, no son recomendables para reducir el uso de nicotina (recomendación débil). 5) Respecto de los pacientes con TDAH y cualquier TUS, el uso de los psicoestimulantes es recomendable para mejorar los síntomas de TDAH (recomendación débil), no para reducir el uso de sustancias (recomendación débil) o para mejorar la retención del tratamiento (recomendación fuerte). En estos pacientes, el uso de atomexetina es recomendable para mejorar los síntomas de TDAH (recomendación débil), no para reducir el uso de sustancias (recomendación débil) o para mejorar la retención del tratamiento (recomendación fuerte). La atomoxetina y los psicoestimulantes parecen ser seguros en pacientes con cualquier TUS (recomendación fuerte). Nuestra revisión sugiere la necesidad de realizar más investigaciones en esta área y de estudios aleatorizados, multicéntricos y de mayor tamaño muestral para proporcionar más evidencia definitiva y concluyente.

Impact of previous tobacco use with or without cannabis on first psychotic experiences in patients with first-episode psychosis.

OBJECTIVE: There is high prevalence of cigarette smoking in individuals with first-episode psychosis (FEP) prior to psychosis onset. The purpose of the study was to determine the impact of previous tobacco use with or without cannabis on first psychotic experiences in FEP and the impact of this use on age of onset of symptoms, including prodromes. METHODS: Retrospective analyses from the naturalistic, longitudinal, multicentre, "Phenotype-Genotype and Environmental Interaction. Application of a Predictive Model in First Psychotic Episodes (PEPs)" Study. The authors analysed sociodemographic/clinical data of 284 FEP patients and 231 matched healthy controls, and evaluated first psychotic experiences of patients using the Symptom Onset in Schizophrenia Inventory. RESULTS: FEP patients had significantly higher prevalence of tobacco, cannabis, and cocaine use than controls. The FEP group with tobacco use only prior to onset (N = 56) had more sleep disturbances (42.9% vs 18.8%, P = 0.003) and lower prevalence of negative symptoms, specifically social withdrawal (33.9% vs 58%, P = 0.007) than FEP with no substance use (N = 70), as well as lower prevalence of ideas of reference (80.4% vs 92.4%, P = 0.015), perceptual abnormalities (46.4% vs 67.4%, P = 0.006), hallucinations (55.4% vs 71.5%, P = 0.029), and disorganised thinking (41.1% vs 61.1%, P = 0.010) than FEP group with previous tobacco and cannabis use (N = 144). FEP patients with cannabis and tobacco use had lower age at first prodromal or psychotic symptom (mean = 23.73 years [SD = 5.09]) versus those with tobacco use only (mean = 26.21 [SD = 4.80]) (P = 0.011). CONCLUSIONS: The use of tobacco alone was not related to earlier age of onset of a first psychotic experience, but the clinical profile of FEP patients is different depending on previous tobacco use with or without cannabis.

Factors associated with alcohol and tobacco consumption as a coping strategy to deal with the coronavirus disease (COVID-19) pandemic and lockdown in Spain.

AIM: To provide a population-based characterization of sociodemographic and clinical risk and protective factors associated with consumption of alcohol, tobacco, or both as a coping strategy in a sample of the Spanish general population during the early phase of the COVID-19 pandemic. METHODS: Cross-sectional study based on an online snowball recruiting questionnaire. The survey consisted of an ad hoc questionnaire comprising clinical and sociodemographic information and the Spanish versions of the Depression, Anxiety, and Stress Scale (DASS-21) and the Impact of Event Scale (IES). RESULTS: The final sample included 21,207 individuals [mean age (SD) = 39.7 (14.0); females: 14,768 (69.6%)]. Up to 2867 (13.5%) of participants reported using alcohol, 2545 (12%) tobacco and 1384 (6.5%) both substances as a strategy to cope with the pandemic. Sex-related factors were associated with alcohol consumption as a coping strategy [female, OR = 0.600, p < 0.001]. However, education level, work status, and income played different roles depending on the substance used to cope. Having a current mental disorder was associated only with tobacco consumption as a coping strategy [OR = 1.391, p < 0.001]. Finally, sex differences were also identified. CONCLUSIONS: Sociodemographic, clinical, and psychological factors were associated with consumption of alcohol, tobacco, or both as a coping method for the COVID-19 pandemic and lockdown. Our findings may help develop specific intervention programs reflecting sex differences, which could minimize negative long-term outcomes of substance use after this pandemic.

Factors associated with tobacco consumption in patients with depression. / Factores asociados con consumo de tabaco en pacientes con depresión.

Smoking and depression are related in a bidirectional way: smoking is the primary avoidable cause of illness and death in patients with depression, and depression is one of the most consistent risk factors for smoking. The main objective of this study is to investigate the relationship between smoking and depression, analyzing sociodemographic and clinical variables such as severity of symptoms, subtype of affective disorder, and its impact on suicidal behavior in the clinical population.A sample of 201 patients, over 18 years of age [mean age (SD) = 53.76 (10.36) years; women = 132 (65.7%)], with a history of depressive episode (unipolar or bipolar) or dysthymia (ICD 10 criteria) was studied.Current smoking prevalence was 43.2% and life-time prevalence 61.2%. No statistically significant differences in smoking prevalence between men and women were found (X2 = 3.896, p = 0.143). The average age of onset was 17.81 (5.60) years. There was a tendency towards a linear association between number of cigarettes/day consumed and severity of depression according to the Hamilton Depression Scale (HDRS) in current smokers (Pearson's R = 0.298, p = 0.050). Multinomial logistic regression analysis showed that current tobacco consumption was associated with higher HDRS scores, with each additional point on the HDRS increasing the likelihood of smoking by 0.062 [p = 0.032; OR (95% CI) = 1.064 (1.005-1.125)].Our results showed that depressed patients present higher prevalence of current smoking than the general population, also suggesting a relationship between severity of consumption and severity of depressive symptoms.

Tabaquismo y depresión se relacionan de forma bidireccional: el tabaquismo es la primera causa evitable de enfermedad y muerte en pacientes con depresión, y la depresión constituye uno de los factores de riesgo de tabaquismo más consistentes. El principal objetivo del presente trabajo es profundizar en la relación entre tabaquismo y depresión, analizando variables socio-demográficas y clínicas como la gravedad de los síntomas, el subtipo de trastorno afectivo, y su impacto en las conductas suicidas en población clínica.Se estudió una muestra de 201 pacientes, mayores de 18 años [edad media (SD) = 53,76 (10,36) años; mujeres = 132 (65,7%)], con historia de episodio depresivo (unipolar o bipolar) o distimia (criterios CIE 10).La prevalencia de tabaquismo actual fue 43,2% y la prevalencia vida 61,2%, no existiendo diferencias estadísticamente significativas entre hombres y mujeres (X2 = 3,896; p = 0,143). La edad media de inicio fue 17,81 (5,60) años. Se observó tendencia a asociación lineal entre número de cigarrillos/día consumidos y gravedad de la depresión según la Escala de Hamilton para la Depresión (HDRS) en los consumidores actuales de tabaco (R de Pearson = 0,298; p = 0,050). El análisis de regresión logística multinomial puso de manifiesto que el consumo actual de tabaco se asocia con puntuaciones más elevadas en la HDRS, de modo que cada incremento de un punto en dicha escala, la posibilidad de fumar aumenta en 0,062 [p = 0,032; OR (95% CI) = 1,064 (1,005-1,125)].Nuestros resultados muestran que los pacientes deprimidos presentan mayor prevalencia de consumo actual de tabaco que la población general, sugiriendo además una relación entre gravedad de consumo y gravedad de los síntomas de depresión.

Can interleukin-2 and interleukin-1ß be specific biomarkers of negative symptoms in schizophrenia? / ¿Pueden ser la interleucina-2 y la interleucina-1ß biomarcadores específicos de la sintomatología negativa en la esquizofrenia?

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-1ß, 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-1ß 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-1ß is not specific to this dimension as it also predicts severity of general and global symptomatology.

Oxidative stress biomarkers and clinical dimensions in first 10 years of schizophrenia. / 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.

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.

Pathological Internet Use and Risk-Behaviors among European Adolescents.

Risk-behaviors are a major contributor to the leading causes of morbidity among adolescents and young people; however, their association with pathological Internet use (PIU) is relatively unexplored, particularly within the European context. The main objective of this study is to investigate the association between risk-behaviors and PIU in European adolescents. This cross-sectional study was conducted within the framework of the FP7 European Union project: Saving and Empowering Young Lives in Europe (SEYLE). Data on adolescents were collected from randomized schools within study sites across eleven European countries. PIU was measured using Young's Diagnostic Questionnaire (YDQ). Risk-behaviors were assessed using questions procured from the Global School-Based Student Health Survey (GSHS). A total of 11,931 adolescents were included in the analyses: 43.4% male and 56.6% female (M/F: 5179/6752), with a mean age of 14.89 ± 0.87 years. Adolescents reporting poor sleeping habits and risk-taking actions showed the strongest associations with PIU, followed by tobacco use, poor nutrition and physical inactivity. Among adolescents in the PIU group, 89.9% were characterized as having multiple risk-behaviors. The significant association observed between PIU and risk-behaviors, combined with a high rate of co-occurrence, underlines the importance of considering PIU when screening, treating or preventing high-risk behaviors among adolescents.

Risk-behaviour screening for identifying adolescents with mental health problems in Europe.

Indicated prevention of mental illness is an important public health concern among youth. The aim of this study was to establish a European school-based professional screening among adolescents, which included variables on both a broad range of risk-behaviours and psychopathology; and to investigate the indicative value of adolescent risk-behaviour and self-reported psychopathology on help-seeking and psychological problems that required subsequent mental healthcare. A two-stage professional screening approach was developed and performed within the multi-centre study "Saving and Empowering Young Lives in Europe" (SEYLE). The first stage of screening comprised a self-report questionnaire on a representative sample of 3,070 adolescents from 11 European countries. In the second stage, students deemed at-risk for mental health problems were evaluated using a semi-structured clinical interview performed by healthcare professionals. 61 % of participants (n = 1,865) were identified as being at-risk in stage one. In stage two, 384 participants (12.5 % of the original sample) were found to require subsequent mental healthcare during semi-structured, clinical assessment. Among those, 18.5 % of pupils were identified due to screening for psychopathology alone; 29.4 % due to screening for risk-behaviours alone; and 52.1 % by a combination of both. Young age and peer victimization increased help-seeking, while very low body mass index, depression, suicidal behaviour and substance abuse were the best predictors of referral to mental healthcare. Screening of risk-behaviours significantly increased the number of detected students requiring subsequent mental healthcare. Screening of risk-behaviours added significant value in identifying the significant amount of European pupils with mental health problems. Therefore, attention to adolescent risk-behaviours in addition to psychopathology is critical in facilitating prevention and early intervention. Identifying factors that increase compliance to clinical interviews are crucial in improving screening procedures.

Adolescent subthreshold-depression and anxiety: psychopathology, functional impairment and increased suicide risk.

BACKGROUND: Subthreshold-depression and anxiety have been associated with significant impairments in adults. This study investigates the characteristics of adolescent subthreshold-depression and anxiety with a focus on suicidality, using both categorical and dimensional diagnostic models. METHODS: Data were drawn from the Saving and Empowering Young Lives in Europe (SEYLE) study, comprising 12,395 adolescents from 11 countries. Based on self-report, including Beck Depression Inventory-II (BDI-II), Zung Self-Rating Anxiety Scale (SAS), Strengths and Difficulties Questionnaire (SDQ) and Paykel Suicide Scale (PSS) were administered to students. Based on BDI-II, adolescents were divided into three groups: nondepressed, subthreshold-depressed and depressed; based on the SAS, they were divided into nonanxiety, subthreshold-anxiety and anxiety groups. Analyses of Covariance were conducted on SDQ scores to explore psychopathology of the defined groups. Logistic regression analyses were conducted to explore the relationships between functional impairments, suicidality and subthreshold and full syndromes. RESULTS: Thirty-two percent of the adolescents were subthreshold-anxious and 5.8% anxious, 29.2% subthreshold-depressed and 10.5% depressed, with high comorbidity. Mean scores of SDQ of subthreshold-depressed/anxious were significantly higher than the mean scores of the nondepressed/nonanxious groups and significantly lower than those of the depressed/anxious groups. Both subthreshold and threshold-anxiety and depression were related to functional impairment and suicidality. CONCLUSIONS: Subthreshold-depression and subthreshold-anxiety are associated with an increased burden of disease and suicide risk. These results highlight the importance of early identification of adolescent subthreshold-depression and anxiety to minimize suicide. Incorporating these subthreshold disorders into a diagnosis could provide a bridge between categorical and dimensional diagnostic models.

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.

Polymorphisms of the IL-1 gene complex are associated with alcohol dependence in Spanish Caucasians: data from an association study.

BACKGROUND: There is growing evidence for involvement of pro-inflammatory cytokines in alcohol dependence. The aim of this study was to investigate whether 4 functionally relevant polymorphisms of the interleukin-1 (IL-1) and tumor necrosis factor-alpha genes were associated with alcohol dependence and with measures of clinical severity and treatment outcome. METHODS: Two hundred alcohol-dependent (AD) patients and 420 healthy controls from the same Spanish Caucasian population were genotyped using standard methods. Baseline and 6-month assessments included alcohol intake, addiction severity, and biomarkers of alcohol intake. RESULTS: Alcohol-dependent patients showed an excess of IL-1alpha-889 C/T [50.8% vs. 39.3%, chi(2) (df) = 7.30 (2), uncorrected p = 0.026, corrected p = 0.104] and IL-1RA (86 bp)(n) A1/A1 genotypes [64.8% vs. 50.8%, chi(2) (df) = 12.65 (3), corrected p = 0.020]. The A1/A1 excess was associated with alcohol dependence only in men [69.9% vs. 49.5%, chi(2) (df) = 15.72 (2), corrected p < 0.001]. Six-month clinical and hematological outcome measures did not vary by genotype of the 4 polymorphisms. Haplotype analysis revealed an excess of the IL-1alpha-889 C/IL-1beta +3953 C/IL-1RA A2 haplotype in the control group compared with AD patients [20.0% vs. 14.1%, chi(2) (df) = 7.25 (1), p = 0.007; odds ratio (OR) = 0.64, 95% confidence interval (CI) = 0.46-0.89] and in the abstainers after 6 months of treatment compared with nonabstinent patients [14.7% vs. 6.2%, chi(2) (df) = 5.65 (1), p = 0.017; OR = 2.56, 95% CI = 1.15-5.62]. CONCLUSIONS: Our findings provide further tentative evidence of the role of IL-1 in alcohol dependence as well as evidence that the nature of the associations may be direct, gender-specific, or involve haplotype effects. However, findings from single association studies constitute tentative knowledge and must be interpreted carefully and precise replication is required.

Differential role of serotonergic polymorphisms in alcohol and heroin dependence.

BACKGROUND: Twin studies suggest that genetic factors account for 40-60% of the variance in alcohol dependence. It has been stated that different drug dependencies may have unique genetic influences. Alterations in serotonin availability and function can affect drinking behaviour. This study aimed to investigate whether three serotonergic polymorphisms (HTR2A A-1438G (rs6311), and SCL6A4 5-HTTLPR and STin2 VNTR) were associated with alcohol dependence, and, whether the serotonergic polymorphisms played a similar role in conferring vulnerability in alcohol and heroin dependence. METHODS: 165 alcohol dependent patients, 113 heroin dependent patients, and 420 healthy controls from a homogeneous Spanish Caucasian population were genotyped using standard methods. RESULTS: Genotypic frequencies of the A-1438G, 5-HTTLPR, and STin2 VNTR polymorphisms did not differ significantly across the three groups. None of the three polymorphisms contributed to distinguishing alcoholic patients from healthy controls. There was an excess of -1438G and 5-HTTLPR L carriers in alcoholic patients in comparison to the heroin dependent group (OR (95% CI)=1.98 (1.13-3.45) and 1.92 (1.07-3.44), respectively). The A-1438G and 5-HTTLPR polymorphisms also interacted in distinguishing alcohol from heroin dependent patients (Wald (df)=10.21 (4), p=0.037). The association of -1438A/G with alcohol dependence was especially pronounced in the presence of 5-HTTLPR S/S, less evident with 5-HTTLPR L/S and not present with 5-HTTLPR L/L. SCL6A4 polymorphism haplotypes were similarly distributed in all three groups. CONCLUSIONS: Our data do not support a role of serotonergic polymorphisms in alcohol dependence but suggest a differential genetic background to alcohol and heroin dependence.

Cardiovascular risk in patients with bipolar disorder.

BACKGROUND: To date, little is known about cardiovascular risk (CVR) in terms of coronary heart disease (CHD) and cardiovascular mortality risk (CMR) in patients with bipolar disorder. This study provides data on the overall risk of any fatal or non-fatal coronary heart disease (CHD) and on the cardiovascular mortality risk (CMR) within 10 years in these patients. METHODS: Naturalistic, cross-sectional, multicenter study conducted in Spain. Patients were evaluated for cardiovascular risk using the Framinghan function (CHD) and the Systematic COronary Risk Evaluation (SCORE) function (CMR). RESULTS: The mean age was 46.6 years and 49% were male. Forty-six percent were in remission. Ten-year CHD risk was 7.6% (males 10.2% versus females 4.7%, p<0.001) and 10-year CMR was 1.8% (males 2.2% versus females 1.3%, p 0.161). Fifty-one percent smoked and 34% was obese. Metabolic syndrome was present in 22.4% of the sample (35.6% according to AHA and NHLBI criteria). Cardiovascular risk significantly increases with age, body mass index and presence of metabolic syndrome. LIMITATIONS: The cross-sectional design of the study. CONCLUSIONS: Cardiovascular risk is high in patients with bipolar disorder. It is associated with age, body mass index and metabolic syndrome. Psychiatrists should be aware of this issue and carefully monitor these patients for cardiovascular risk factors, including cigarette smoking, as part of the standard of care when treating them.