Impact of cognitive reserve in clinical, neurocognitive and lifestyle factors in chronic schizophrenia and early stages of schizophrenia.

INTRODUCTION: Although there is evidence that higher cognitive reserve (CR) is a protective factor and it has been related to better prognosis, there have been no studies to date that have explored the CR level and its impact in clinical, neurocognitive and lifestyle outcomes according to the stage of the disease: early stage of psychosis (ESP) or chronic schizophrenia (SCZ). MATERIAL AND METHODS: A total of 60 patients in the ESP and 225 patients with SCZ were enrolled in the study. To test the predictive capacity of CR for each diagnostic group, a logistic regression analysis was conducted. Hierarchical linear regression analyses were performed to explore the associations between CR and different outcomes. The mediation analyses were performed according to the principles of Baron and Kenny. RESULTS: Patients with SCZ showed lower CR than those in the ESP (p<0.001). CR correctly classified 79.6% of the cases (p<0.001; Exp(B)=1.062). In ESP group, CR was related to working memory (p=0.030) and negative symptoms (p=0.027). CR (t=3.925, p<0.001) and cannabis use (t=2.023, p=0.048) explained 26.7% of the variance on functioning (p=0.003). In patients with SCZ, CR predicted all cognitive domains, negative symptoms (R2=0.091, p=0.001) and functioning (R2=0.074, p=0.005). In both ESP and SCZ groups, higher CR was associated with lower body mass index and circumference. In ESP group, the effect of adherence to Mediterranean diet on functioning (p=0.037) was mediated by CR level (p=0.003). CONCLUSIONS: The implications of CR depend on the stage of the disease (ESP vs. SCZ), with a greater effect on neurocognition and negative symptoms in patients with chronic SCZ.

From gut to brain: A network model of intestinal permeability, inflammation, and psychotic symptoms in schizophrenia.

Impaired intestinal permeability has recently been suggested as a possible source of chronic inflammation in schizophrenia, but its association with specific psychopathological features remains uncertain. This study aimed to explore the interaction between intestinal permeability, inflammation, and positive and negative symptoms in schizophrenia using a network analysis approach. The study sample comprised 281 adults with schizophrenia (age 40.29 ± 13.65 years, 63.0 % males), enrolled in a cross-sectional observational study assessing intestinal permeability. We estimated the network with a Gaussian graphical model, incorporating scores from 14 individual items of the Positive and Negative Syndrome Scale (PANSS), along with body mass index (BMI), and plasma C-reactive protein (CRP) and lipopolysaccharide-binding protein (LBP) levels. We calculated strength centrality and expected influence and used bridge centrality statistics to identify the bridge nodes. Distinct but highly interconnected clusters emerged for positive and negative symptoms. The biological variables were closely associated with each other. LBP was positively linked with CRP and BMI, but only indirectly connected to psychopathology. CRP exhibited direct positive relationships with various PANSS items and bridged LBP and BMI with psychopathology. Bridge nodes included Conceptual Disorganisation (P2), Active Social Avoidance (G16), Suspiciousness/Persecution (P6), and CRP. These findings support the role of gut-derived inflammation as a mechanism underlying greater symptom severity in schizophrenia and emphasise the importance of addressing dietary habits not only to enhance physical health but also to contribute to improving psychotic symptoms.

Spanish validation of the Empirically Developed Clinical Staging Model (EmDe-5) for patients with bipolar disorder.

INTRODUCTION: Bipolar disorder (BD) has been reconceptualised as a progressive disorder that develops from mild to severe presentations. An empirical staging model - the Empirically Developed Clinical Staging Model for BD (EmDe-5) - was developed in a previous study. This study aims to further validate that model using a larger and more representative Spanish sample. MATERIAL AND METHODS: 183 BD outpatients were recruited at 11 sites in Spain. Assessment included clinical characteristics of the BD (number of hospitalisations, number of suicide attempts, comorbid personality disorders), physical health (BMI, metabolic syndrome, number of physical illnesses), cognition (SCIP), functioning (permanently disabled due to BD, FAST), and quality of life (SF-36). The CGI-S, VAS-S, and psychopharmacological treatment pattern were used as external validators. RESULTS: Ten patients (51.5%) were classified as stage 1, 33 (18%) as stage 2, 93 (508%) as stage 3, 37 (202%) as stage 4, and 10 (55%) as stage 5. All profilers, other than number of suicide attempts (p=0.311) and comorbid personality disorder (p=0.061), exhibited worse scores from stage 1 to 5. As expected, VAS-S and CGI-S scores were worse in the later stages. Regarding treatment, early stages (1-2) were associated with the use of one to three drugs while late stages (4-5) were associated with four or more drugs (p=0.002). CONCLUSIONS: We confirm the EmDe-5 staging model's construct validity. The ease of obtaining the profilers, together with the operational criteria provided to quantify them, will facilitate the use of the EmDe-5 staging model in daily clinical practice.

Intestinal permeability and low-grade chronic inflammation in schizophrenia: A multicentre study on biomarkers. Rationale, objectives, protocol and preliminary results.

BACKGROUND: Altered intestinal permeability and low-grade chronic inflammation disrupt the integrity of the blood-brain barrier (microbiota-gut-brain axis), probably playing a role in the pathophysiology of schizophrenia-spectrum disorders. However, studies assessing the microbiota-gut-brain axis are inconsistent. This article describes the rationale, objectives, protocol, and presents descriptive results for a new project. METHODS: The sample of this study came from an observational, cross-sectional and multisite study including four centers in Spain (PI17/00246) recruiting adult patients with DSM-5 schizophrenia-spectrum disorders at any stage of the disease. The aims of the project are to assess the interrelation between intestinal permeability and low-grade chronic inflammation in schizophrenia-spectrum disorders and the role of peripheral biomarkers, diet, exercise, metabolic syndrome, disease severity and functioning as well as cognition. Assessments included the following variables: (1) anthropometric, (2) intestinal permeability, diet, and physical exercise, (3) clinical and functional, (4) neuropsychological and cognitive reserve, and (5) peripheral biomarkers from blood. RESULTS: A total of 646 patients were enrolled (257, 39.7% female). Mean age was 43.2±13.6 years, illness duration 15.1±11.5 years. 55.8% consumed tobacco. Positive PANSS score was 13.68±6.55, and 20.38±8.69 in the negative symptoms. CGI was 4.16±2.22 and GAF was 60.00±14.84. CONCLUSION: The results obtained by this project are expected to contribute toward the understanding of the physiopathology of schizophrenia-spectrum disorders. This will likely aid to personalize treatments in real-world clinical practice, potentially including variables related to intestinal permeability and inflammation.

Maternity in women with schizophrenia and schizoaffective disorder.

PURPOSE: Maternity rates in women with schizophrenia have tripled in the past decades, with a current percentage similar to the general population (50-60%). However, mothers with schizophrenia present higher rates of single marital status, and social dysfunction than the general population. In addition, the incidence of unplanned pregnancy, abortions, miscarriages and obstetric complications is higher. This study aimed to describe variables related to maternity in this population. METHODS: One-hundred and ninety-two outpatient women diagnosed with schizophrenia and schizoaffective disorders were included (DSM-IV-TR criteria) in a two-site study. Psychosocial risk factors, demographic variables and clinical features were recorded in the same visit. Non-parametric tests were used in order to describe variables for likelihood offspring in psychotic women. RESULTS: One-hundred and forty-seven (76.6%) women suffered from schizophrenia and 45 (23.4%) schizoaffective disorder. Psychotic mothers used to be married/having a partner and presented a later onset of the illness (over 36 years old) compared to non-mothers. In addition, mothers generally presented pregnancy before the onset of illness. Regarding obstetric complications, around the 80% of the sample presented at least one obstetric complication. Although desire or wish of pregnancy was reported in 66.3% of the mothers, rates of planned pregnancy were 25% and only the 47.9% were currently taking care of their children with their husband/partner. CONCLUSION: Maternity rate is high in this population. This study highlights the need to promote reproductive health care for women with mental disorders and to consider their reproductive life plan. Later onset of disease and being married are potential predictors of maternity in our sample of women with a schizophrenia and schizoaffective disorders while only the half were caring their children at the moment of the evaluation.

Association between neutrophil-lymphocyte ratio, platelet-lymphocyte ratio, and C-reactive protein levels and metabolic status in patients with a bipolar disorder.

OBJECTIVES: Neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), and C-Reactive Protein (CRP) are markers of inflammation that are elevated in bipolar disorder (BD) and are also related to a higher risk of metabolic syndrome (MetS). This study aimed at investigating for the first time the association between NLR, PLR, and CRP and the metabolic status in BD. METHODS: We assessed the association between biomarkers and the metabolic status: number of metabolic risk factors, presence of MetS, insulin sensitivity (Quantitative Insulin Sensitivity Check Index, QUICKI) and insulin resistance (Homeostatic Model Assessment for Insulin Resistance, HOMA-IR index), in a sample of 219 outpatients with BD. RESULTS: 25.9% of the sample met the criteria for MetS. High levels of CRP were found in 12% of the sample. Older age, low PLR, high NLR, and high CRP levels significantly predicted a higher number of MetS risk factors (p < 0.001). Older age and low PLR were associated with a greater likelihood of developing MetS (p = 0.007). CONCLUSIONS: Although further studies are needed to replicate and validate these findings, inflammatory biomarkers as CRP, PLR and NLR could be useful tools to identify patients with a BD at risk for a metabolic adverse outcome.

Clozapine and paliperidone palmitate antipsychotic combination in treatment-resistant schizophrenia and other psychotic disorders: A retrospective 6-month mirror-image study.

BACKGROUND: Around 30% of patients with schizophrenia are considered treatment resistant (TRS). Only around 40% of TRS patients respond to clozapine. Long acting injectable antipsychotics could be a useful augmentation strategy for nonresponders. METHODS: We conducted a multicenter, observational, naturalistic, retrospective, 6-month mirror-image study to evaluate the efficacy and tolerability of clozapine and paliperidone palmitate association in 50 patients with TRS and other psychotic disorders. Clinical outcomes and side effects were systematically assessed. RESULTS: Six months after starting the combined treatment, participants showed a significant relief of symptoms, decreasing the Brief Psychiatric Rating Scale total score from 18.32 ± 7.71 to 7.84 ± 5.16 (p < 0.001). The number of hospitalizations, the length of hospital stays and the number of visits to emergency services also decreased, while an increase of the functionality was observed (Personal and Social Performance total score increased from 46.06 ± 118.7 to 60.86 ± 18.68, p < 0.001). There was also a significant decrease in the number and severity of side effects with the combination therapy, decreasing the Udvalg for Kliniske Undersogelser total score from 10.76 ± 8.04 to 8.82 ± 6.63 (p = 0.004). CONCLUSIONS: This study provides the first evidence that combining clozapine with paliperidone palmitate in patients with TRS and other psychotic disorders could be effective and safe, suggesting further research with randomized controlled trials of augmentation strategies for clozapine nonresponder patients. POLICY SIGNIFICANCE STATEMENT: Patients with psychotic disorders such as schizophrenia show a variable response to antipsychotic treatments. Around 30% of patients are considered treatment resistant, indicated by insufficient symptom control to at least two different drugs. In these resistant cases, clozapine should be indicated, as it has shown to be superior to other options. However, only 40% of patients respond to clozapine, being necessary to establish which treatments could best potentiate clozapine action. Combining clozapine with long acting injectable antipsychotics, and particularly paliperidone palmitate, could be a useful strategy. We conducted a multicenter study of 50 patients with treatment-resistant schizophrenia and other psychotic disorders comparing the efficacy and tolerability in the 6 month-period prior and after starting the clozapine and paliperidone palmitate association. Our study suggests that this combination could be effective and safer, laying the groundwork for future clinical trials with this combination.

Corrigendum: A Multicenter Phase II RCT to Compare the Effectiveness of EMDR Versus TAU in Patients With a First-Episode Psychosis and Psychological Trauma: A Protocol Design.

[This corrects the article DOI: 10.3389/fpsyt.2019.01023.].

Sexual Dysfunction and Mood Stabilizers in Long-Term Stable Patients With Bipolar Disorder.

BACKGROUND: In addition to factors intrinsic to bipolar disorder (BD), sexual functioning (SF) can be affected by extrinsic causes, such as psychotropic drugs. However, the effect of mood stabilizers on SF and quality of life (QoL) is an underexplored research area. AIM: To analyze SF in BD outpatients in euthymia for at least 6 months treated only with mood stabilizers and the association between SF and QoL. METHODS: A multicenter cross-sectional study was conducted in 114 BD outpatients treated with (i) lithium alone (L group); (ii) anticonvulsants alone (valproate or lamotrigine; A group); (iii) lithium plus anticonvulsants (L+A group); or (iv) lithium plus benzodiazepines (L+B group). The Changes in Sexual Functioning Questionnaire Short Form (CSFQ-14) was used. Statistical analyses were performed to compare CSFQ-14 scores among the pharmacological groups. An adaptive lasso was used to identify potential confounding variables, and linear regression models were used to study the association of the CSFQ-14 with QoL. MAIN OUTCOME MEASURES: Self-reports on phases of the sexual response cycle (ie, desire, arousal, and orgasm) and QoL were assessed. RESULTS: The A group had better total SF scores than the L group and the L+B group. Relative to the A group, the L and L+B groups had worse sexual desire; the L group had worse sexual arousal; and the L+A group and the L+B group had worse sexual orgasm. Regarding sociodemographic factors, being female and older age were associated with worse total SF and all subscale scores. Among all subscales scores, higher sexual arousal scores were associated with better QoL. CLINICAL IMPLICATIONS: Potential modified extrinsic factors such as psychotropic medication that can affect SF can be addressed and adjusted to lessen side effects on SF. STRENGTHS & LIMITATIONS: Sample of patients with euthymic BD in treatment with mood stabilizers and no antipsychotics or antidepressants, substance use as an exclusion criterion, and use of a validated, gender-specific scale to evaluate SF. Major limitations were cross-sectional design, sample size, and lack of information about stability of relationship with partner. CONCLUSIONS: Lithium in monotherapy or in combination with benzodiazepines is related to worse total SF and worse sexual desire than anticonvulsants in monotherapy. While the addition of benzodiazepines or anticonvulsants to lithium negatively affects sexual orgasm, sexual arousal (which plays a significant role in QoL) improves when benzodiazepines are added to lithium. Anticonvulsants in monotherapy have the least negative effects on SF in patients with BD. García-Blanco A, García-Portilla MP, Fuente-Tomás L de la, et al. Sexual Dysfunction and Mood Stabilizers in Long-Term Stable Patients With Bipolar Disorder. J Sex Med 2020;17:930-940.

A clinical staging model for bipolar disorder: longitudinal approach.

Bipolar disorder (BD) has been identified as a life-course illness with different clinical manifestations from an at-risk to a late stage, supporting the assumption that it would benefit from a staging model. In a previous study, we used a clustering approach to stratify 224 patients with a diagnosis of BD into five clusters based on clinical characteristics, functioning, cognition, general health, and health-related quality of life. This study was design to test the construct validity of our previously developed k-means clustering model and to confirm its longitudinal validity over a span of 3 years. Of the 224 patients included at baseline who were used to develop our model, 129 (57.6%) reached the 3-year follow-up. All life domains except mental health-related quality of life (QoL) showed significant worsening in stages (p < 0.001), suggesting construct validity. Furthermore, as patients progressed through stages, functional decline (p < 0.001) and more complex treatment patterns (p = 0.002) were observed. As expected, at 3 years, the majority of patients remained at the same stage (49.6%), or progressed (20.9%) or regressed (23.3%) one stage. Furthermore, 85% of patients who stayed euthymic during that period remained at the same stage or regressed to previous stages, supporting its longitudinal validity. For that reason, this study provides evidence of the construct and longitudinal validity of an empirically developed, comprehensive staging model for patients with BD. Thus, it may help clinicians and researchers to better understand the disorder and, at the same time, to design more accurate and personalized treatment plans.

Sex differences in bipolar disorder: Impact of lifetime cannabis use on clinical course, functioning, and quality of life in bipolar disorder.

BACKGROUND: Cannabis use is markedly prevalent among patients with bipolar disorder (BD). However, to date, there have been no studies on this issue with a sex-based approach. This study examines if lifetime cannabis use (LCU) is differently associated with clinical course, functioning, and quality of life (QoL) in patients with BD by sex. METHODS: Secondary analysis of a cross-sectional, naturalistic, multicentre study. LCU was defined as having had at least one day of use per month for at least 12 consecutive months in a patient's life. RESULTS: A total of 224 patients with BD were included (65.2% women). Patients with LCU were younger (p = 0.001) and had their first hospitalization earlier (p<0.005) than those without LCU, regardless of sex. Among women, LCU was associated with being single (p = 0.006), worse sexual functioning (p = 0.006), financial functioning (p = 0.009), QoL [bodily pain (p = 0.009), vitality (p = 0.027), social functioning (p = 0.037), emotional role (p = 0.038), mental health (p = 0.001), and mental summary component (p = 0.012)]. After controlling for confounders, among women, LCU was associated with worse QoL, specifically on bodily pain (p = 0.049) and mental health (p = 0.016) subscales. Among males, no statistically significant differences were found between LCU and no LCU (NLCU) in any of the variables of the study. LIMITATIONS: This study was a secondary analysis not powered specifically to analyze cannabis use. CONCLUSIONS: LCU was associated with a younger age at first hospitalization in both women and men, while only women reported worse QoL on bodily pain and mental health subscales. Clinicians and public health providers should be aware of this and inform their patients and the general population of these detrimental effects.

Cognitive Reserve Assessment Scale in Health (CRASH): Its Validity and Reliability.

(1) Background: The cognitive reserve (CR) concept has not been precisely defined in severe mental disorders and has been estimated using heterogeneous methods. This study aims to investigate and develop the psychometric properties of the Cognitive Reserve Assessment Scale in Health (CRASH), an instrument designed to measure CR in people with severe mental illness; (2) Methods: 100 patients with severe mental illness (non-affective psychoses and affective disorders) and 66 healthy controls were included. The internal consistency and convergent validity of CRASH were assessed. Spearman's correlations coefficients were also performed to examine the relationship between CRASH and neuropsychological tests, psychosocial functioning, and clinical course; (3) Results: The internal consistency was high (Cronbach's alpha coefficient = 0.903). The CRASH global score had a large positive correlation with the Cognitive reserve questionnaire total score (r = 0.838, p < 0.001), demonstrating good convergent validity. The correlation coefficients between the CRASH total scores and clinical, functional, and neuropsychological performance were different between groups. In order to provide clinical interpretation, severity classification based on diagnosis (non-affective psychotic disorders, affective disorders, and healthy controls) have been created; (4) Conclusions: CRASH is the first CR measure developed specifically for patients with severe mental illness, facilitating reliable and valid measurement of this construct. The scale may aid in the stratification of patients and the implementation of personalized interventions.

Are plasma 25-hydroxyvitamin D and retinol levels and one-carbon metabolism related to metabolic syndrome in patients with a severe mental disorder?

There is a scarcity of studies assessing the influence of biomarkers in metabolic syndrome in psychiatric patients. Our aim was to correlate serum or plasma levels of 25-hydroxyvitamin D (25-OH-VD), retinol, vitamin B12 (VB12), folate and homocysteine (Hcy), with the metabolic status, in a sample of 289 outpatients with Schizophrenia or Bipolar Disorder. Logistic regression and multiple linear regressions were performed to assess the ability of biomarkers to predict the presence of MetS, the number of risk factors for MetS, and insulin resistance indexes (HOMA and QUICKI). Regarding the association between biomarkers and the QUICKI index, the model explained 6.8% of the variance, with folate and 25-OH-VD levels contributing significantly to the model. The model predicting the number of MetS risk factors was significant and explained 21.7% of the variance, being 25-OH-VD and retinol the statistically significant factors. As for the impact of biomarkers on MetS, the model was statistically significant, being 25-OH-VD and retinol levels the significant factors.  We report for the first time an association between MetS and both low 25-OH-VD and high retinol concentrations. Inflammation-related biomarkers may help identify patients with a high risk of MetS who might benefit from healthy lifestyle counselling and early intervention.

Classification of patients with bipolar disorder using k-means clustering.

INTRODUCTION: Bipolar disorder (BD) is a heterogeneous disorder needing personalized and shared decisions. We aimed to empirically develop a cluster-based classification that allocates patients according to their severity for helping clinicians in these processes. METHODS: Naturalistic, cross-sectional, multicenter study. We included 224 subjects with BD (DSM-IV-TR) under outpatient treatment from 4 sites in Spain. We obtained information on socio-demography, clinical course, psychopathology, cognition, functioning, vital signs, anthropometry and lab analysis. Statistical analysis: k-means clustering, comparisons of between-group variables, and expert criteria. RESULTS AND DISCUSSION: We obtained 12 profilers from 5 life domains that classified patients in five clusters. The profilers were: Number of hospitalizations and of suicide attempts, comorbid personality disorder, body mass index, metabolic syndrome, the number of comorbid physical illnesses, cognitive functioning, being permanently disabled due to BD, global and leisure time functioning, and patients' perception of their functioning and mental health. We obtained preliminary evidence on the construct validity of the classification: (1) all the profilers behaved correctly, significantly increasing in severity as the severity of the clusters increased, and (2) more severe clusters needed more complex pharmacological treatment. CONCLUSIONS: We propose a new, easy-to-use, cluster-based severity classification for BD that may help clinicians in the processes of personalized medicine and shared decision-making.

A Multicenter Phase II RCT to Compare the Effectiveness of EMDR Versus TAU in Patients With a First-Episode Psychosis and Psychological Trauma: A Protocol Design.

Background: Patients with a first episode psychosis (FEP) who are admitted for the first time to a psychiatric hospital frequently have experienced prior psychological trauma. Additionally, 40-80% develop posttraumatic stress symptoms, which are summarized as a post-psychotic post-traumatic syndrome (PPS). Eye Movement Desensitization and reprocessing (EMDR) therapy could be an effective psychotherapy to treat a PPS and prior psychological traumas in this population. Objectives: To assess if EMDR therapy leads to: 1) a reduction of relapses after intervention, 2) an improvement of trauma-related, psychotic and affective symptoms, 3) an improvement of overall functioning, and 4) an improvement in quality of life. Methods: This is a multicenter phase II rater-blinded randomized controlled trial in which 80 FEP patients with a history of psychological trauma will be randomly assigned to EMDR (n = 40) or to TAU (n = 40). Traumatic events will be measured by the Global Assessment of Posttraumatic Stress Questionnaire, the Cumulative Trauma Screening, the Impact of Event Scale-Revised, the Dissociative Experiences Scale, the Childhood Trauma Scale, the Holmes-Rahe Life Stress Inventory, and the Dissociative Experiences Questionnaire. Clinical symptomatology will be evaluated using the Suicide and Drug Consumption module of the International Neuropsychiatric Interview, Structured Clinical Interview for Positive and Negative Syndrome Scale, Young's Scale for Mania Evaluation, and Beck Depression II Questionnaire. Functionality will be assessed with the Global Assessment of Functioning and the Quality of Life with the Standardized Instrument developed by the EuroQol Group. The cognitive insight and adherence to the treatment will be assessed with the Beck Cognitive Insight Scale and the Drug Attitude Inventory. All variables will be measured at baseline, post-treatment and at 12-month follow-up. Conclusion: This study will provide evidence of whether EMDR therapy is effective in reducing trauma and clinical symptoms, reducing relapses and in improving functionality and quality of life in patients with FEP and a history of trauma. Clinical Trial Registration: www.ClinicalTrials.gov, identifier: NCT03991377.

Sleep disturbances, functioning, and quality of life in euthymic patients with bipolar disorder.

There is scarce knowledge about the impact of sleep disturbances on functioning and quality of life (QoL). This study aims to investigate the links between sleep satisfaction and duration, and functioning and QoL in euthymic BD patients. We made a secondary analysis of a cross-sectional, naturalistic, multicenter study. Inclusion criteria: DSM-IV BD diagnosis; age > 17 years; written informed consent. Sample: 119 Spanish euthymic BD outpatients. Hierarchical multiple regressions were performed controlling for confounding factors. We found that almost half of the patients reported at least one sleep complaint, nighttime awakenings (60.5%) and difficulty falling asleep (31.9%) were the most frequent. Long sleep duration was associated with worse global functioning, and also with worse occupational functioning along with caffeine consumption. Sleep satisfaction was negatively associated with worse QoL in the mental health subscale and the summary mental. In both cases, the use of benzodiazepines negatively affects these QoL domains. In conclusion, euthymic bipolar patients frequently present sleep disturbances that seem to contribute to the impairment of their functioning and QoL. Also, the use of benzodiazepines negatively affects the QoL of these patients. Thus, a detailed sleep evaluation should be performed, and the use of benzodiazepines should be reduced to the minimum.

1st International Experts' Meeting on Agitation: Conclusions Regarding the Current and Ideal Management Paradigm of Agitation.

Agitation is a heterogeneous concept without a uniformly accepted definition, however, it is generally considered as a state of cognitive and motor hyperactivity characterized by excessive or inappropriate motor or verbal activity with marked emotional arousal. Not only the definition but also other aspects of agitated patients' care are still unsolved and need consensus and improvement. To help the discussion about agitation among experts and improve the identification, management, and treatment of agitation, the 1st International Experts' Meeting on Agitation was held in October 2016 in Madrid. It was attended by 20 experts from Europe and Latin America with broad experience in the clinical management of agitated patients. The present document summarizes the key conclusions of this meeting and highlights the need for an updated protocol of agitation management and treatment, the promotion of education and training among healthcare professionals to improve the care of these patients and the necessity to generate clinical data of agitated episodes.

Are affective temperaments determinants of quality of life in euthymic patients with bipolar disorder?

BACKGROUND: Bipolar disorder (BD) is a disabling illness that is associated with low quality of life (QoL). This low QoL goes further than mood episodes, which suggests that stable traits, such as affective temperaments, can cause functional impairment. OBJECTIVE: Our study analyses the impact of affective temperaments on the Physical Component Summary (PCS) and Mental Component Summary (MCS) of QoL in euthymic BD patients. METHODS: A multicentre study was conducted in 180 euthymic BD patients and 95 healthy controls. Firstly, statistical analyses were performed to compare QoL and affective temperaments between the two groups. Secondly, Adaptive Lasso Analysis was carried out to identify the potential confounding variables and select the affective temperaments as potential predictors on the PCS and MCS of QoL in BD patients, as well as the control group. RESULTS: QoL scores in terms of PCS and MCS in BD patients were significantly lower than in healthy individuals. Whereas anxious temperament, anxiety disorder comorbidity, and age were the best predictors of PCS impairment in BD patients, anxious temperament, subclinical depressive symptoms, and age were the best predictors of MCS impairment. LIMITATIONS: Further longitudinal studies with unaffected high-risk relatives are needed to examine the potential interaction between affective temperament and psychopathology. CONCLUSIONS: Anxious temperament has an impact on QoL in BD in terms of both the physical component and the mental component. Systematic screening of temperament in BD would give clinicians better knowledge of QoL predictors. Further research should allow more individualized treatment of BD patients based on temperamental factors.

Documento de posicionamiento de consenso por el Colectivo de Psiquiatras por la Actualización de Clozapina / Consensus position document by the Clozapine Update Psychiatrists Group

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Substance Use in Patients With First-Episode Psychosis: Is Gender Relevant?

OBJECTIVE: Only a few studies in patients with first-episode psychosis have included gender in the study hypothesis or considered this a primary study variable. The aim of this study was to explore the influence of gender in the pattern of substance use in patients with first-episode psychosis. METHODS: This is a sub-analysis of a randomized open clinical trial that compared 1-year treatment retention rates of patients with first-episode psychosis randomized to haloperidol, olanzapine, quetiapine, risperidone, or ziprasidone. Our sub-analysis included 85 men and 29 women. RESULTS: Substance use was relatively high among these patients and differed significantly by gender. Men were more likely to use substances overall than women (89.4% for men vs. 55.2% for women), χ(2) = 16.2, df = 1, p <.001, and were also more likely to use alcohol (χ(2) = 13, df = 1, p <.001), cannabis (χ(2) = 9.9; df = 1, p <.002), and cocaine (χ(2) = 10.3; df = 1, p <.001), compared to women. While there were no gender differences in age at first consumption of alcohol or cocaine, men were significantly younger at first consumption of cannabis (M = 16.08 years, SD = 2.1) than women (M = 18.0 years, SD = 3.8), F(1, 59) = 5, p <.02. When analyzed separately by gender, women showed no significant differences in the influence of number of substances used on age at onset of psychosis, F(3, 29) = 1.2, p =.30. However, there was a significant difference among men, with earlier onset of psychosis noted in men consuming multiple substances; F(4, 85) = 5.8, p <.0001. Regarding prediction of age at onset of psychosis, both male gender and the use of a higher number of substances significantly predicted an earlier age at onset of psychosis. CONCLUSIONS: Our study provides some evidence of gender differences in the pattern of substance use in patients with first-episode psychosis, suggesting the possible need for gender-specific approaches in the interventions performed in these patients. This study is registered as #12610000954022 with the Australian New Zealand Clinical Trials Registry (www.anzctr.org.au).