A Systematic Review on the Association between Schizophrenia and Bipolar Disorder with Chronic Obstructive Pulmonary Disease.

A systematic review aimed to investigate the association between schizophrenia and bipolar disorder and chronic obstructive pulmonary disease (COPD), its prevalence and incidence, potential factors associated with its occurrence and its impact on mortality among these patients. We performed the literature search in PubMed, Scopus and PsycInfo from inception to February 2022 and identified 19 studies: ten cross-sectional, 5 that included cross-sectional and longitudinal analyses, and 4 retrospective cohort studies. The reported prevalence of COPD ranged from 2.6% to 52.7% in patients with schizophrenia and between 3.0% and 12.9% in patients with bipolar disorder. Two studies reported an annual incidence of COPD of 2.21 cases/100 person-years in patients with schizophrenia and 2.03 cases/100 person-years in patients with bipolar disorder. Among the risk factors evaluated in three studies, only advanced age was consistently associated with the presence/occurrence of COPD in patients with schizophrenia and bipolar disorder; the role of tobacco consumption was not investigated in those three studies. According to two studies, the likelihood of mortality from COPD showed an over 3-fold increase in patients with schizophrenia and a 2-fold increase in those with bipolar disorder compared to the overall population; COPD was also associated with increased inpatient mortality. Available data indicate that COPD in patients with schizophrenia and bipolar disorder is a major public health problem. National and international health organizations should strive to specifically address this issue by creating awareness about this health problem and developing specific programs for screening and early intervention aimed to reduce the burden of COPD in these populations.

The Multi-Component Smoking Cessation Support Programme (McSCSP) is effective in patients with severe mental disorder without gender differences. / El programa multicomponente de apoyo para el cese del tabaquismo (McSCSP) es efectivo en pacientes con trastorno mental grave sin diferencias de género.

High prevalence of smoking in people with severe mental disorders (SMD) contributes to their medical morbidity and reduced life expectancy. Despite the evidence of gender differences in smoking cessation, few studies have tested those differences among people with SMD. This is a non-randomized, open-label, prospective, 9-month follow-up multicentre trial to examine gender differences in the efficacy, safety and tolerability of a Multi-Component Smoking Cessation Support Programme (McSCSP). The results showed that there were no significant differences in short- (males 44.9% vs females 57.7%, chi-square = 1.112, p = 0.292) or long-term efficacy (week 24: males 40.8%, females 42.3%, chi-square = 0.016, p = 0.901; week 36: males 36.7%, females 38.5%, chi-square = 0.022, p = 0.883) between gender, neither controlled by diagnosis or treatment. Regarding safety and tolerability, there was significant increase in abdominal perimeter in males [from 105.98 (SD 13.28) to 108.52 (SD 14.01), t = -3.436, p = 0.002)], but not in females. However, there were no significant gender differences in adverse events (constipation, abnormal/vivid dreams, nausea/vomiting or skin rash/redness around patch site). In conclusion, we have demonstrated that is effective and safe to help either male or female patients with stabilized SMD to quit smoking. However, it might be a tendency in females to respond better to varenicline treatment in the short-term. Future research with larger samples is required to more clearly determine whether or not the there are differences, in addition to their reliability and robustness.

La elevada prevalencia del tabaquismo en personas con trastorno mental grave (TMG) contribuye a su morbilidad médica y reduce su esperanza de vida. A pesar de la existencia de diferencias de género en el cese del tabaquismo, pocos estudios han evaluado esas diferencias en personas con TMG. Este es un ensayo multicéntrico de seguimiento prospectivo, no aleatorizado, abierto de 9 meses para examinar las diferencias de género en la eficacia, seguridad y tolerabilidad de un programa multicomponente de apoyo para el cese del tabaquismo (McSCSP). Los resultados mostraron que no hubo diferencias de género significativas en la eficacia a corto (hombres 44,9% vs mujeres 57,7%, chi cuadrado = 1,112, p = ,292) ni a largo plazo (semana 24: hombres 40,8%, mujeres 42,0.3%, chi cuadrado = 0.016, p = ,901; semana 36: hombres 36,7%, mujeres 38,5%, chi cuadrado = 0,022, p = ,883), incluso controlando por diagnóstico o tratamiento.  Con respecto a la seguridad y la tolerabilidad, hubo un aumento significativo en el perímetro abdominal en los hombres [de 105,98 (DT 13,28) a 108,52 (DT 14,01), t = -3,436, p = ,002)], pero no en las mujeres. Sin embargo, no hubo diferencias de género significativas en los eventos adversos (estreñimiento, sueños anormales/vívidos, náuseas/vómitos o erupción cutánea/enrojecimiento alrededor de la zona del parche). En conclusión, hemos demostrado que es efectivo y seguro ayudar a los hombres y mujeres con TMG estabilizados a dejar de fumar.  Sin embargo, podría haber una tendencia en las mujeres a responder mejor al tratamiento con vareniclina a corto plazo. Se requiere investigación futura con muestras más amplias para determinar con más claridad la existencia de diferencias, además de la fiabilidad y robustez.

Setting the stage to quit smoking in Bipolar Disorder patients: brief advice in clinical practice. / Preparando el escenario para dejar de fumar en el paciente con Trastorno Bipolar: intervención breve en la práctica clínica.

Tobacco consumption is the main preventable factor of mortality in smokers with bipolar disorder (BD), and any possible solutions are often blocked by prejudices over desire, and the possibilities and risks for these patients in giving up tobacco consumption. Adults with BD were recruited at 8 Mental Health Centres. Smokers were evaluated before and after a brief intervention based on the 3 A's and classified into a 'Stage of Change' (SOC) and their 'Readiness to Change' (RTC). A multiple linear regression was used to analyze the progression in their RTC and the independent effect of different variables (pharmacological treatment, history of psychotic symptoms, current anxiety symptoms, willingness, self-perceived capacity to quit smoking and subjective perception of cognitive functioning). Of 212 stable patients diagnosed with BD, current smokers (n=101; 47.6%) were included in the intervention phase, and 80.2% completed it. At baseline, 75.2% were considering the idea of giving up smoking and, after the brief intervention, 30.9% of the patients progressed in their SOC. A significant increase in the level of RTC was observed (53.3 vs 59.3, P=0.019). Perception of cognitive performance (ß=-0.35;P=0.002), the degree of willing to quit (ß=0.32;P=0.008), self-perceived capacity to quit tobacco smoking (ß=-0.30;P=0.012), the patient's age (ß=-0.72;P=0.004), the age of onset of smoking (ß=0.48;P=0.022) and years as a smoker (ß=0.48;P=0.025) were all factors that significantly influenced the chances of improving after the short intervention. Smokers with BD consider the idea of quitting and a brief intervention developed in the every day mental health care setting improves the level of readiness. The neurocognitive dysfunction associated with BD may limit patients' readiness to quit smoking.

El consumo de tabaco es el principal factor prevenible de mortalidad en pacientes con trastorno bipolar (TB), y las posibles soluciones se encuentran bloqueadas por prejuicios acerca del deseo, posibilidades y riesgos al dejar el consumo de tabaco en estos pacientes. En 8 Centros de Salud Mental se reclutaron consecutivamente pacientes con TB. Los fumadores fueron evaluados antes y después de una intervención breve basada en las 3 As y clasificados según los "estadios de cambio" (EC) y su "disposición para el cambio" (DC). Mediante una regresión lineal múltiple se analizó la evolución del DC y su efecto sobre otras variables independientes (tratamiento farmacológico, historias de síntomas psicóticos, presencia de síntomas de ansiedad, deseo de abandono, capacidad auto-percibida y la percepción subjetiva de funcionamiento cognitivo). Se incluyeron 212 pacientes con TB estabilizados, los fumadores activos (n=101; 47.6%) pasaron a la fase de intervención, y un 80.2% la completaron. Basalmente, 75.2% consideraban la idea de dejar de fumar, después de la intervención breve, el 30.9% de los pacientes progresó en su EC. Se observó un incremento significativo del nivel de DC (53.3 vs 59.3, P=0.019). La autopercepción del rendimiento cognitivo (ß=-0.35;P=0.002), el deseo de abandono (ß=0.32;P=0.008), la autopercepción de la capacidad para dejar de fumar (ß=-0.30;P=0.012), la edad del paciente (ß=-0.72;P=0.004), la edad de inicio del tabaquismo (ß=0.48;P=0.022) y los años fumando (ß=0.48;P=0.025) fueron los factores que influyeron significativamente en la posibilidad de cambio tras la intervención breve. Los fumadores con TB consideran la idea de dejar de fumar y una intervención breve desarrollada en el marco de la atención a la salud mental diaria, mejoraría el nivel de preparación. La disfunción neurocognitiva asociada con el TB podría limitar la disposición de los pacientes a dejar de fumar.

Low lung function in Bipolar Disorder and Schizophrenia: a hidden risk.

Introduction: People with serious mental illness (SMI), such as schizophrenia and bipolar disorder, have a higher risk of premature morbidity and mortality. In the general population, impaired lung function is associated with increased morbidity and mortality. We compared lung function between people with and without serious mental illnesses using a cross-sectional study in 9 community mental health units. Methods: Subjects aged 40-70 years with a diagnosis of schizophrenia or bipolar disorder were recruited consecutively. The controls had no psychiatric diagnosis and were not receiving any psychotropics. Spirometry was performed by a trained nurse. We used the 2021 American Thoracic Society/European Respiratory Society standards for the interpretation of the spirometry results. Results: We studied 287 subjects. People with SMI (n = 169) had lower spirometry values than those without a psychiatric diagnosis (n = 118). An abnormal spirometry pattern (36.1% vs 16.9%, p < 0.001), possible restriction or non-specific (Preserved Ratio Impaired Spirometry [PRISm]) pattern (17.8% vs 7.6%, p = 0.014), and pattern of airflow obstruction or possible mixed disorder (18.3% vs 9.3%, p = 0.033) were more frequent in people with SMI. Multivariate analyses showed that the PRISm pattern was associated with abdominal circumference (odds ratio [OR] 1.05, 95%CI 1.03-1.08) and that the pattern of airflow obstruction or possible mixed disorder was associated with smoking behavior (OR 5.15, 95%CI 2.06-15.7). Conclusion: People with SMI have impaired lung function, with up to one-third of them showing an abnormal spirometry pattern. This suggests that regular monitoring of lung function and addressing modifiable risk factors, such as tobacco use and obesity, in this population is of paramount importance.

Efficacy of clozapine versus standard treatment in adult individuals with intellectual disability and treatment-resistant psychosis (CLOZAID): study protocol of a multicenter randomized clinical trial.

Background: Intellectual disability (ID) affects approximately 1% of the worldwide population and individuals with ID have a higher comorbidity with mental illness, and specifically psychotic disorders. Unfortunately, among individuals with ID, limited research has been conducted since ID individuals are usually excluded from mental illness epidemiological studies and clinical trials. Here we perform a clinical trial to investigate the effectiveness of clozapine in the treatment of resistant psychosis in individuals with ID. The article highlights the complexity of diagnosing and treating psychopathological alterations associated with ID and advocates for more rigorous research in this field. Methods: A Phase IIB, open-label, randomized, multicenter clinical trial (NCT04529226) is currently ongoing to assess the efficacy of oral clozapine in individuals diagnosed with ID and suffering from treatment-resistant psychosis. We aim to recruit one-hundred and fourteen individuals (N=114) with ID and resistant psychosis, who will be randomized to TAU (treatment as usual) and treatment-with-clozapine conditions. As secondary outcomes, changes in other clinical scales (PANSS and SANS) and the improvement in functionality, assessed through changes in the Euro-QoL-5D-5L were assessed. The main outcome variables will be analyzed using generalized linear mixed models (GLMM), assessing the effects of status variable (TAU vs. Clozapine), time, and the interaction between them. Discussion: The treatment of resistant psychosis among ID individuals must be directed by empirically supported research. CLOZAID clinical trial may provide relevant information about clinical guidelines to optimally treat adults with ID and treatment-resistant psychosis and the benefits and risks of an early use of clozapine in this underrepresented population in clinical trials. Trial registration: Clinicaltrials.gov: NCT04529226. EudraCT: 2020-000091-37.

Spanish HCMV Seroprevalence in the 21st Century.

Human cytomegalovirus (HCMV) is linked to age-related diseases like cardiovascular disease, neurodegenerative conditions, and cancer. It can also cause congenital defects and severe illness in immunocompromised individuals. Accurate HCMV seroprevalence assessment is essential for public health planning and identifying at-risk individuals. This is the first HCMV seroprevalence study conducted in the general Spanish adult population in 30 years. We studied HCMV seroprevalence and HCMV IgG antibody titres in healthy adult donors (HDs) and HCMV-related disease patients from 2010 to 2013 and 2020 to 2023, categorized by sex and age. We compared our data with 1993 and 1999 studies in Spain. The current HCMV seroprevalence among HDs in Spain is 73.48%. In women of childbearing age, HCMV seroprevalence has increased 1.4-fold in the last decade. HCMV-seropositive individuals comprise 89.83% of CVD patients, 69% of SMI patients, and 70.37% of COVID-19 patients. No differences in HCMV seroprevalence or HCMV IgG antibody titres were observed between patients and HDs. A significant reduction in Spanish HCMV seroprevalence among HDs was observed in 1993. However, women of childbearing age have shown an upturn in the last decade that may denote a health risk in newborns and a change in HCMV seroprevalence trends.

Psychometric properties of the Spanish version of the Body Weight, Image and Self-Esteem Evaluation Questionnaire in patients with severe mental disorders.

OBJECTIVE: Clinicians need brief and valid instruments to monitor the psychosocial impact of weight gain in persons with psychiatric disorders. We examined the psychometric properties of the Spanish version of the Body Weight, Image and Self-Esteem Evaluation (B-WISE) questionnaire in patients with severe mental disorders. METHOD: The data come from a naturalistic, cross-sectional, validation study conducted at 6 centres in Spain. A total of 211 outpatients with severe mental disorders, 118 with schizophrenia and 93 with bipolar disorder, were evaluated using the B-WISE, the Visual Analogue Scale for Weight and Body Image, and the Clinical Global Impression-Severity (CGI-S). The body mass index was also obtained. RESULTS: The principal component analysis confirms 3 components explaining 50.93% of the variance. The Cronbach α values for B-WISE scales ranged between .55 and .73. Significant Pearson correlations were found between B-WISE total score and CGI-S (r = -0.25; P < .001) and Visual Analogue Scale for Weight and Body Image (r = 0.47; P < .001). The B-WISE discriminates among patients with mild, moderate, and severe mental disorders according to CGI-S scores (F = 6.52; P < .005). Body mass index categorization significantly influenced total B-WISE scores (F = 3.586, P < .050). The B-WISE score corresponding to the 5th and 10th percentiles was 22. CONCLUSIONS: We were able to demonstrate that the Spanish version of the B-WISE is a valid instrument for assessing psychosocial impact of weight gain in patients with severe mental disorders in daily clinical practice.

Psychometric properties of the Spanish version of the Changes in Sexual Functioning Questionnaire Short-Form (CSFQ-14) in patients with severe mental disorders.

INTRODUCTION: Sexual dysfunction in patients with severe mental disorders is often underestimated or overlooked by psychiatrists. A brief and valid self-report instrument for assessing sexual functioning may well contribute to changing this situation. AIMS: To validate the Short Form of the Changes in Sexual Functioning Questionnaire (CSFQ-14) in Spanish patients with severe mental disorders. METHODS: Naturalistic, cross-sectional, multicenter, validation study. Eighty-nine patients with schizophrenia and 82 with bipolar disorder were evaluated using the CSFQ-14, the Visual Analogue Scale for Sexual Functioning Satisfaction (VAS-SFS), and the Clinical Global Impression-Severity scales for mental disorders (CGI-S) and for Sexual Dysfunction (CGI-SSD). MAIN OUTCOME MEASURES: The 14-item Changes in Sexual Functioning Questionnaire. RESULTS: Internal reliability (Cronbach's alpha) = 0.90. Construct validity = 3 principal components, of which the first, arousal-orgasm, explained 46.4% of the total variance. Convergent validity: Pearson correlation coefficients between CSFQ-14 and VAS-SFS = 0.33 (P < 0.01) and between CSFQ-14 and CGI-SDS = -0.71 (P < 0.01). Discriminant validity: The CSFQ-14 was able to discriminate among patients with no, mild, moderate, and severe sexual dysfunction according to CGI-SDS scores, both in males (P < 0.001) and females (P < 0.001). In males, the area under the curve (AUC) was 0.833 and a cutoff point of 49 provided a sensitivity of 92.9% and a specificity of 59.5%. In females, the AUC was 0.834 and a cutoff point of 43 provided a sensitivity of 91.9% and a specificity of 62.5%. CONCLUSION: The Spanish version of the CSFQ-14 is a reliable and valid instrument for assessing sexual functioning in patients with severe mental disorders. As a brief, self-rated instrument, the CSFQ-14 scale seems to be appropriate for use in everyday clinical practice as a means of identifying and monitoring changes in sexual functioning.

Gut microbiota, innate immune pathways, and inflammatory control mechanisms in patients with major depressive disorder.

Although alterations in the gut microbiota have been linked to the pathophysiology of major depressive disorder (MDD), including through effects on the immune response, our understanding is deficient about the straight connection patterns among microbiota and MDD in patients. Male and female MDD patients were recruited: 46 patients with a current active MDD (a-MDD) and 22 in remission or with only mild symptoms (r-MDD). Forty-five healthy controls (HC) were also recruited. Psychopathological states were assessed, and fecal and blood samples were collected. Results indicated that the inducible nitric oxide synthase expression was higher in MDD patients compared with HC and the oxidative stress levels were greater in the a-MDD group. Furthermore, the lipopolysaccharide (an indirect marker of bacterial translocation) was higher in a-MDD patients compared with the other groups. Fecal samples did not cluster according to the presence or the absence of MDD. There were bacterial genera whose relative abundance was altered in MDD: Bilophila (2-fold) and Alistipes (1.5-fold) were higher, while Anaerostipes (1.5-fold) and Dialister (15-fold) were lower in MDD patients compared with HC. Patients with a-MDD presented higher relative abundance of Alistipes and Anaerostipes (1.5-fold) and a complete depletion of Dialister compared with HC. Patients with r-MDD presented higher abundance of Bilophila (2.5-fold) compared with HC. Thus, the abundance of bacterial genera and some immune pathways, both with potential implications in the pathophysiology of depression, appear to be altered in MDD, with the most noticeable changes occurring in patients with the worse clinical condition, the a-MDD group.

Lifestyle in Undergraduate Students and Demographically Matched Controls during the COVID-19 Pandemic in Spain.

Few studies have used a multidimensional approach to describe lifestyle changes among undergraduate students during the COVID-19 pandemic or have included controls. This study aimed to evaluate lifestyle behaviors and mental health of undergraduate students and compare them with an age and sex-matched control group. A cross-sectional web survey using snowball sampling was conducted several months after the beginning of COVID-19 pandemic in Spain. A sample of 221 students was recruited. The main outcome was the total SMILE-C score. Students showed a better SMILE-C score than controls (79.8 + 8.1 vs. 77.2 + 8.3; p < 0.001), although these differences disappeared after controlling for covariates. While groups did not differ in the screenings of depression and alcohol abuse, students reported lower rates of anxiety (28.5% vs. 37.1%; p = 0.042). A lower number of cohabitants, poorer self-perceived health and positive screening for depression and anxiety, or for depression only were independently associated (p < 0.05) with unhealthier lifestyles in both groups. History of mental illness and financial difficulties were predictors of unhealthier lifestyles for students, whereas totally/moderate changes in substance abuse and stress management (p < 0.05) were predictors for the members of the control group. Several months after the pandemic, undergraduate students and other young adults had similar lifestyles.

Lifestyle changes and mental health during the COVID-19 pandemic: A repeated, cross-sectional web survey.

BACKGROUND: This study aimed to compare self-reported changes on lifestyle behaviors during two phases of the COVID-19 pandemic in Spain, and to evaluate clinical and sociodemographic factors associated with lifestyles. METHODS: Two cross-sectional web surveys were conducted during lockdown (April 15-May 15, 2020) and seven months later (November 16-December 16, 2020). Lifestyle behaviors were self-reported by a multidimensional scale (SMILE-C). Two separate samples of respondents were analyzed. A multivariate regression model was performed to evaluate the association of SMILE-C scores with demographic and clinical variables. RESULTS: The sample comprised, 3412 participants from the first survey (S1) and in the S1 and 3635 from the second (S2). SMILE-C score decreased across surveys (p < 0.001). The rates of positive screenings for depression and anxiety were similar between the surveys, whereas those for alcohol abuse decreased (p < 0.001). Most participants in S2 reported that their lifestyle had not changed compared to those before the pandemic. Variables independently associated with an unhealthier lifestyle were working as an essential worker, lower educational level, previous mental disease, worse self-rated health, totally/moderate changes on diet, sleep or social support, as well as positive screenings for alcohol abuse, anxiety and depression. LIMITATIONS: The cross-sectional design and recruitment by non-probabilistic methods limit inferring causality and the external validity of the results. CONCLUSIONS: Overall lifestyle worsened seven months after the lockdown in Spain. Several demographic and clinical factors were associated with lifestyle scores. The contribution of common mental disorders to unhealthier lifestyles should be considered in order to prevent the negative impact of the pandemic.

Voxel-based morphometry comparison between first episodes of psychosis with and without evolution to schizophrenia.

First episodes (FE) of psychosis may evolve or not to schizophrenia in ensuing years, but there is a lack of reliable predictors of which patients will have to face such an unfavorable outcome. Given the replicated structural alterations of the brain in schizophrenia, it seems advisable to assess whether the alterations of this kind that can be detected at the time of an initial psychotic episode are different depending on the outcome of the patients. To this end, here we applied voxel-based morphometry to assess whether the degree of cerebral abnormalities differ between 30 FE patients who evolved to schizophrenia in the ensuing 2years and another 14 FE patients who could not be diagnosed as such during that period. Forty-one controls were also included in the study. We found that the FE patients who evolved to schizophrenia had a significantly lower GM value than the controls bilaterally in the left dorsolateral prefrontal (BA 9) and in left anterior cingulate (BA 33) regions while the FE patients who did not develop schizophrenia showed a distinct, right-sided pattern of deviation (visual cortex, superior temporal gyrus and inferior frontal). The direct comparison between FE patients who evolved or not evolved to schizophrenia did not reveal significant differences. Taken together, our results support the notion that brain abnormalities may be different in psychotic FE patients depending on their evolution in the medium term.

Association between cerebral metabolic and structural abnormalities and cognitive performance in schizophrenia.

The possible association in schizophrenia between frontal abnormalities, such as hypofrontality and frontal grey matter (GM) deficits, and neuropsychological deficits is not yet well defined. Our objective was to study such an association and to clarify the cognitive relevance of metabolic and anatomical variability across schizophrenia patients. To do so, we studied dorsolateral prefrontal (DLPF) metabolism during an attention test using fluoro-deoxy-glucose positron emission tomography and DLPF structure with magnetic resonance imaging (MRI) in 22 schizophrenia patients [9 neuroleptic-naïve (NN) first episodes]. These patients also underwent a comprehensive battery of neuropsychological tests aimed at evaluating global intelligence and the proposed domains of cognitive alteration in schizophrenia, i.e., attention, visual and verbal learning and memory, working memory, problem solving and processing speed. The metabolic activity in the right DLPF region was significantly and directly related to processing speed, and a measure of structural deficit in the same area was directly related to working memory scores. In the NN group studied alone, these associations were replicated. We may conclude that hypofrontality during cognitive activation, and the degree of DLPF structural deficit may be associated to a particular profile of cognitive deficit, including lower processing speed and working memory capacity.

Smoking cessation opportunities in severe mental illness (tobacco intensive motivational and estimate risk - TIMER-): study protocol for a randomized controlled trial.

BACKGROUND: There is an increased risk of premature death in people with severe mental illness (SMI). Respiratory disorders and cardiovascular disease are leading causes of increased mortality rates in these patients, and tobacco consumption remains the most preventable risk factor involved. Developing new tools to motivate patients towards cessation of smoking is a high priority. Information on the motivational value of giving the lung age and prevention opportunities is unknown in this high-risk population. METHODS/DESIGN: This article describes in detail a protocol developed to evaluate an intensive motivational tool, based on the individual risks of pulmonary damage and prevention opportunities. It is designed as a randomized, 12-month, follow-up, multicenter study. A minimum of 204 smokers will be included, aged 40 years and older, all of whom are patients diagnosed with either schizophrenia or bipolar disorder (BD). Chronic obstructive pulmonary disease (COPD) will be evaluated using spirometry, and the diagnosis will then be validated by a pneumologist and the lung age estimated. Based on this value, a motivational message about prevention will be issued for the intervention group, which will be reinforced by individualized text messages over a period of 3 months. The efficacy of the method and the pulmonary damage variables will be evaluated: smoking cessation at the end of follow-up will be confirmed by cooximetry, and the COPD diagnosis and the severity of the staging for disease will be assessed. DISCUSSION: In the context of community care, screening and early detection of lung damage could potentially be used, together with mobile technology, in order to produce a prevention message, which may provide patients with SMI with a better chance of quitting smoking. TRIAL REGISTRATION: ClinicalTrials.gov, ID: NCT03583203 . Registered on 11 July 2018. Trial status: recruitment.

Identification of two clusters within schizophrenia with different structural, functional and clinical characteristics.

BACKGROUND: Several biologically distinct subgroups may coexist within schizophrenia, which may hamper the necessary replicability to translate research findings into clinical practice. METHODS: Cortical thickness, curvature and area values and subcortical volumes of 203 subjects (121 schizophrenia patients, out of which 64 were first episodes), 60 healthy controls and 22 bipolar patients were used to identify clusters using principal components and canonical discriminant analyses. Regional glucose metabolism using positron emission tomography, P300 event related potential, baseline clinical data and percentage of improvement with treatment were used to validate possible clusters based on MRI data. RESULTS: All the controls, the bipolar patients and most of the schizophrenia patients were grouped in a cluster (cluster A). A group of 24 schizophrenia patients (12 first episodes), characterized by large intrinsic curvature values, was identified (cluster B). These patients, but not those in cluster A, showed reduced thalamic and cingulate glucose metabolism in comparison to controls, as well as a worsening of negative symptoms at follow-up. Patients in cluster A showed a significant putaminal metabolic increase, which was not observed for those in cluster B. P300 amplitude was reduced in patients of both clusters, in comparison to controls. CONCLUSIONS: Results of this study support the existence of a biologically distinct group within the schizophrenia syndrome, characterized by increased cortical curvature values, reduced thalamic and cingulate metabolism, lack of the expected increased putaminal metabolism with antipsychotics and persistent negative symptoms.

It is feasible and effective to help patients with severe mental disorders to quit smoking: An ecological pragmatic clinical trial with transdermal nicotine patches and varenicline.

Despite the proven association between smoking and high rates of medical morbidity and reduced life expectancy in people with severe mental disorders (SMD), their smoking rates do not decline as they do in the general population. We carried out a non-randomized, open-label, prospective, 9-month follow-up multicentre trial to investigate the clinical efficacy, safety and tolerability of a 12-week smoking cessation programme for patients with SMD in the community under real-world clinical conditions. Eighty-two adult outpatients with schizophrenic/bipolar disorder smoking ≥15 cigarettes/day were assigned by shared decision between doctors and patients to transdermal nicotine patches (TNP) [36(46.2%)] or varenicline [39(50%)]. Short-term efficacy: The 12-week 7-day smoking cessation (self-reported cigarettes/day=0 and breath carbon monoxide levels≤9ppm) prevalence was 49.3%, without statistically significant differences between medications (TNP 50.0% vs varenicline 48.6%, chi-square=0.015, p=1.000). Long-term efficacy: At weeks 24 and 36, 41.3 and 37.3% of patients were abstinent, with no statistically significant differences between treatments. Safety and Tolerability: no patients made suicide attempts/required hospitalization. There was no worsening on the psychometric scales. Patients significantly increased weight [TNP 1.1(2.8) vs varenicline 2.5(3.3), p=0.063], without significant changes in vital signs/laboratory results, except significant decreases in alkaline phosphatase and low-density lipoprotein-cholesterol levels in the varenicline group. Patients under varenicline more frequently presented nausea/vomiting (p<0.0005), patients under TNP experienced skin reactions more frequently (p=0.002). Three patients under varenicline had elevated liver enzymes. In conclusion, we have demonstrated that in real-world clinical settings it is feasible and safe to help patients with stabilized severe mental disorders to quit smoking.

Increase in gray matter and decrease in white matter volumes in the cortex during treatment with atypical neuroleptics in schizophrenia.

The effects of atypical antipsychotic treatment on the brain volume deficits associated with schizophrenia are poorly understood. We assessed the brain volumes of eleven healthy controls and 29 patients with schizophrenia, using magnetic resonance imaging at baseline and at follow-up after two years of treatment with atypical neuroleptics. Two groups of patients were analyzed: treatment-naïve patients (n = 17) and chronic treatment-resistant patients (n = 12). Treatment-naïve patients received risperidone during the follow-up period, whereas chronic patients received clozapine. Gray matter (GM) and white matter (WM) volumes in the frontal, parietal, occipital, and temporal lobes were measured. Contrary to the controls, both groups of patients presented GM increases and WM decreases in the parietal and occipital lobes (p < .005). Frontal GM also increased in the chronic group with clozapine. There was a significant (p < .001) inverse relationship between the baseline volumes (GM deficit/WM excess) and the longitudinal change. These GM and WM changes were not related to changes in weight. Thus, treatment with risperidone and clozapine in schizophrenia may have an effect on gray and white matter volume and needs further exploration.

N-acetyl-aspartate levels in the dorsolateral prefrontal cortex in the early years of schizophrenia are inversely related to disease duration.

Magnetic resonance spectroscopy studies in schizophrenia have revealed consistently reduced N-acetyl aspartate (NAA) levels in chronic patients, but not in recent-onset patients. Studies on the relationship between this marker and disease duration have commonly been negative, although it is also true that they have been conducted in patients with long-standing disease. We compared NAA levels in the dorsolateral prefrontal cortex in 16 recent-onset patients (duration: 1.8+/-0.6 years), 19 chronic patients (duration: 9.7+/-6.1 years), and 20 healthy controls. We studied the NAA/creatine and choline/creatine ratios in the dorsolateral prefrontal cortex in both hemispheres, controlling for the effect of age. Chronic patients had significantly lower NAA/Cr ratios in the left hemisphere compared to recent-onset patients and healthy controls, with no difference in Cho/Cr ratio. There were no differences between controls and recent-onset patients. There was a significant inverse relationship between left-side NAA/Cr and disease duration, suggesting that prefrontal NAA levels may progressively decrease in schizophrenia. Taken within the context of the existing literature, these results indicate that this process may be limited to the early years following the onset of the disease. Therefore, reduced prefrontal levels of NAA may be limited to chronic schizophrenia patients.

Prefrontal atrophy in first episodes of schizophrenia associated with limbic metabolic hyperactivity.

Reduced volume and activity of the prefrontal (PF) cortical gray matter (GM) and hippocampal hypermetabolism are repeated findings in schizophrenia. There is still an information deficit about the significance of reduction of PF GM in schizophrenia, and a simultaneous study of PF anatomy and activity and limbic metabolism can contribute to fill that deficit. In order to do so, we used positron emission tomography (PET) with 18-fluoro-deoxy-glucose (FDG) during an attention task and magnetic resonance imaging (MRI) to study a sample of first episodes of psychosis. We included 21 first episodes (FE) of psychosis and 16 healthy controls. A diagnosis of schizophrenia was confirmed in the follow-up in eleven of these patients and ruled out in the remaining 10 cases. Volumes of PF GM were determined and also activity in the same region and in the hippocampus. Residual GM was estimated in the PF region as a quantitative measurement of the degree of atrophy in each individual, using age and intracranial volume data from a set of 45 healthy controls and linear regression. Patients with schizophrenia had lower PF metabolic activation and greater hippocampal activity than controls. FE patients without schizophrenia were no different in any parameter as compared to controls. Patients with schizophrenia presented an inverse and significant association between GM deficit and hippocampal activity that was not observed in controls or in patients without schizophrenia. The same association was previously described by our group using PET in the resting state in recent-onset and chronic patients with schizophrenia. These findings support a loss in PF inhibitory capacity as a possible link between anatomical and functional alterations in schizophrenia.