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Introduction: Several international studies show high rates of depression and suicidal ideation in medical students. However, no specific data is available in Spanish students. The aim of this study is to determine the prevalence of depressive symptoms and suicidal ideation in the Faculty of Medicine of Valencia, as well as its relationship with other variables of interest., Methods: In April 2018, all students enrolled in the Medical Degree of the University of Valencia were invited to complete the Beck Depression Inventory (BDI-II). The students participated voluntarily and the answers were anonymized., Results: A total of 858 students (69.2% women) completed the survey (response rate of 44.7%). More than a third of the sample (39.1%) had depressive symptoms, of mild to severe intensity, while 15.8% of the students reported recent suicidal ideation. Significantly higher levels of depressive symptoms were found in women, as well as in those with a worse satisfaction with academic results, a greater perception of the need for psychological support due to recent mental health problems and in those who had ever consulted with health professionals for a mental health problem (29.4%)., Conclusions: These results are consistent with the prevalence of depression in medical students from other countries and suggest comparative studies in other Spanish universities. Medical schools should incorporate interventions to provide students with tools that improve their mental health.

Background: Scarce research has focused on Visual Memory (VM) deficits as a possible neurocognitive endophenotype of bipolar disorder (BD). The main aim of this longitudinal, family study with healthy controls was to explore whether VM dysfunction represents a neurocognitive endophenotype of BD., Methods: Assessment of VM by Rey-Osterrieth Complex Figure Test (ROCF) was carried out on a sample of 317 subjects, including 140 patients with BD, 60 unaffected first-degree relatives (BD-Rel), and 117 genetically-unrelated healthy controls (HC), on three occasions over a 5-year period (T1, T2, and T3). BD-Rel group scores were analyzed only at T1 and T2., Results: Performance of BD patients was significantly worse than the HC group (p < 0.01). Performance of BD-Rel was also significantly different from HC scores at T1 (p < 0.01) and T2 (p = 0.05), and showed an intermediate profile between the BD and HC groups. Only among BD patients, there were significant differences according to sex, with females performing worse than males (p = 0.03). Regarding other variables, education represented significant differences only in average scores of BD-Rel group (p = 0.01)., Limitations: Important attrition in BD-Rel group over time was detected, which precluded analysis at T3., Conclusions: BD patients show significant deficits in VM that remain stable over time, even after controlling sociodemographic and clinical variables. Unaffected relatives also show stable deficits in VM. Accordingly, the deficit in VM could be considered a potential endophenotype of BD, which in turn may be useful as a predictor of the evolution of the disease. Further studies are needed to confirm these findings., (Copyright © 2019. Published by Elsevier B.V.)

Although there is substantial evidence supporting the existence of neurocognitive impairment in patients diagnosed with schizophrenia (SZ) and bipolar disorder (BD), few studies have explored the field from an endophenotypic perspective. The present systematic review sought to identify longitudinal family studies exploring suitable neurocognitive endophenotypes in unaffected relatives of patients with SZ and/or BD. Following the PRISMA statement, only five follow-up studies met the inclusion criteria, comprising 79 SZ patients, 159 SZ unaffected relatives of SZ, 131 BD patients, 77 unaffected relatives of BD, and 248 controls. Verbal memory, auditory attention, face memory and emotion processing were found as putative endophenotypic candidates for SZ, whereas this strategy identified none for BD. Substantial heterogeneity and lack of standardization in global neurocognitive assessment within this area should be pointed out; nevertheless, several candidate endophenotypes were identified for SZ, except for executive impairment., (Copyright © 2019 Elsevier B.V. All rights reserved.)

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 (β=-0.35;P=0.002), the degree of willing to quit (β=0.32;P=0.008), self-perceived capacity to quit tobacco smoking (β=-0.30;P=0.012), the patient's age (β=-0.72;P=0.004), the age of onset of smoking (β=0.48;P=0.022) and years as a smoker (β=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.

Background: Bipolar disorder (BD) is associated with significant neurocognitive and functional impairment, which may progress across stages. However, the potential progression of subjective cognitive complaints and quality of life (QoL) has not been addressed. Our main objective was to assess subjective cognitive complaints and QoL on euthymic patients with BD and their healthy siblings., Methods: Four groups were compared: euthymic patients with type I BD in the early (n = 25) and late (n = 23) stages, their healthy siblings (latent stage; n = 23) and healthy controls (n = 21). Cognitive complaints and QoL were assessed using the COBRA and WHO-QoLBREF questionnaires, respectively., Results: Late-stage patients had greater number of subjective cognitive complaints and reported a worse QoL compared to the other groups. Early-stage patients also had more cognitive complaints than controls and siblings, although differences were not significant. Siblings and controls reported similar QoL., Limitations: the most important limitation of this study is the criterion used to define the early and late stages of BD, as currently there is no consensus and previous studies have used different criteria., Conclusions: This is the first study to examine subjective cognition and QoL in patients with BD and siblings. Our results raise the possibility that burden of cognitive complaints increase with disorder progression, in tandem with deterioration in subjective QoL. That would support a clinical staging model of BD. This hypothesis remains to be confirmed by a longitudinal analysis., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Despite significant advances in pharmacological and non-pharmacological treatments, mood disorders remain a significant source of mental capital loss, with high rates of treatment resistance, requiring a coordinated effort in investigation and development of efficient, tolerable and accessible novel interventions. Ketogenic diet (KD) is a low-carb diet that substantially changes the energetic matrix of the body including the brain. It has been established as an effective anticonvulsant treatment, and more recently, the role of KD for mental disorders has been explored. Ketogenic diet has profound effects in multiple targets implicated in the pathophysiology of mood disorders, including but not limited to, glutamate/GABA transmission, monoamine levels, mitochondrial function and biogenesis, neurotrophism, oxidative stress, insulin dysfunction and inflammation. Preclinical studies, case reports and case series have demonstrated antidepressant and mood stabilizing effects of KD, however, to date, no clinical trials for depression or bipolar disorder have been conducted. Because of its potential pleiotropic benefits, KD should be considered as a promising intervention in research in mood disorder therapeutics, especially in treatment resistant presentations., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Available evidence suggests that nicotine may enhance cognitive functioning. Moreover, it has been suggested that the high prevalence of smoking in people with schizophrenia is in part due to self-medication behaviour to alleviate cognitive deficits. We assessed the association between tobacco smoking and cognitive functioning in a large population of first episode psychosis (FEP) patients (n=304) and healthy controls (n=156). Smokers were not tobacco deprived, or were minimally deprived (≤2h). Verbal memory, visual memory, working memory, processing speed, executive function, motor dexterity and attention were assessed. The smoking prevalence among the FEP group was 57% (n=174). The age at which patients began smoking cigarettes regularly was 16.2years (SD=3.1), an average of 12years before experiencing the first frank symptoms of psychosis (age of onset=28.8; SD=9.3). The number of cigarettes smoked per day was 19.6 (SD=9.4), significantly more than healthy controls [11.0 (SD=7.6); p<0.001]. ANCOVA analysis did not show any significant difference between smokers and non-smokers in in the performance of any of the cognitive tasks in the FEP group or in the healthy control group, independent of gender, age, education or premorbid IQ. This suggests chronic exposure to nicotine through cigarette smoking is not associated with cognitive functioning in first-episode psychosis. These findings do not support the nicotine self-medication hypothesis as a contributor to the high prevalence of smoking among individuals suffering from serious mental illness., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Aims: Changes in serum cytokines and altered neutrophin concentration have been associated with bipolar disorder (BD). Our aim here was to analyze peripheral blood biomarkers according to the clinical stages of BD., Method: Euthymic BD-I patients were grouped according to their level of functioning in early-stage (n=25) and late-stage (n=23), and compared to healthy siblings (n=23) and genetically unrelated healthy controls (n=21). Neurotrophin (neurotrophin-3 and BDNF) concentration and biomarkers of inflammation, including cytokines (IL-6, IL-10 and TNF-α), leukocytes count and acute phase proteins, were measured., Results: IL-10 concentration was significantly increased in early-stage patients compared to late-stage patients, healthy siblings and controls whereas TNF-α concentration was significantly increased in late-stage patients compared to controls. Total leukocytes, neutrophil and monocyte count were significantly increased in late-stage patients compared to healthy siblings and controls. The concentration of IL-6, neurotrophin-3 and BDNF was unchanged in euthymia. Healthy siblings did not show significant changes in any biomarker., Conclusions: The concentration of IL-10, TNF-α, neutrophil and monocytes subtype count in blood is altered in patients with BD during euthymic state. The link between peripheral inflammation and different stages in BD deserves further studies., (Copyright © 2017 Elsevier Inc. All rights reserved.)

We analyzed the efficacy of functional remediation, in a sample of patients with bipolar disorder who presented with subsyndromal symptoms. From a total sample of 239 patients with bipolar I and II disorder, according to DSM-IV-TR diagnostic criteria, entering a randomized clinical trial, those patients who presented with subsyndromal symptoms were selected based on a method already described by Berk and colleagues was applied. It consists of using the Clinical Global Impression-Bipolar version (CGI-BP) to establish the scores of the Hamilton Depression Rating Scale (HAM-D) and of the Young Mania Rating Scale (YMRS) that correspond with 1 in the CGI-BP. Functional outcome and mood symptoms were assessed at 6 and at 12-month follow-up. A total of 99 patients were selected for this post-hoc analysis, allocated as follows: functional remediation (n=33); psychoeducation (n=37) and treatment as usual (TAU,n=29). The repeated-measures analyses at 12-month follow-up revealed a significant group x time interaction in favour of the patients who received functional remediation when compared to psychoeducation and TAU (F=2.93; p=0.02) at improving psychosocial functioning. Finally, mood symptoms did not significantly change in any of the three groups at any time of follow-up, as shown by the non-significant group x time interaction effect in HAM-D scores (F=1.57; p=0.18) and YMRS scores (F=1.51; p=0.20). Bipolar patients with subsyndromal symptoms improve their functional outcome when exposed to functional remediation regardless of the persistence of mood symptomatology., (Copyright © 2017 Elsevier B.V. and ECNP. All rights reserved.)

Purpose: Childbearing age has progressively increased in industrialized countries. The impact of this delay on motherhood, however, requires further research., Methods: The study sample included a prospective cohort of healthy nulliparous pregnant women aged between 18 and 40 years (n=148) assessed at 38 weeks gestation (Time#1, T1), 48h after birth (Time#2, T2), and 3 months after birth (Time#3, T3). The effect of age on psychological, biological, and social variables was evaluated. Maternal psychological symptoms in terms of depression and anxiety were assessed at T1-T3; and parenting stress at T3. Stress biomarkers (cortisol, α-amylase) were determined in mothers at T1-T3. Questionnaires addressing social functioning (i.e., family functioning, maternal attitudes, and social support) were conducted at T3. Bayesian additive models were used to analyze the data., Results: Depressive symptoms showed a steep increase starting from 35 years of age at T1 and an U-shaped relationship with a minimum around 30 years old at T3. The same results were observed for parenting stress. Cortisol levels increased sharply from 30 years of age at T3. Family functioning, maternal attitudes, and social support improved moderately from 30 years of age., Conclusions: Prenatal depressive symptoms were higher in older women, but postpartum depressive symptoms and parenting stress increased in both younger and older women. Nevertheless, cortisol levels just increased in older ages at postpartum. In contrast, social functioning (family functioning, maternal attitudes, and social support) improved with age. We conclude that these social advantages may compensate for other disadvantages of delayed childbearing (i.e., depressive symptoms, parenting stress, and high cortisol level)., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Background: Bipolar disorder (BD) is a serious mental illness associated with a high risk of medical comorbidities, long-term disability and premature death. This systematic review examined the current literature on therapeutic interventions targeting nutrition, physical activity and wellness in BD and collecting health-related measures such as mood and course of illness., Methods: Scopus (all databases), Pubmed and Ovid Medline were systematically searched with no language or year restrictions, up to June 2015, for studies focusing on lifestyle interventions in BD. Search terms were related to bipolar disorder, nutrition, physical activity, wellbeing, psychosocial interventions and course of illness. We hand searched content pages of Bipolar Disorders and Journal of Affective Disorders and checked references of relevant reviews and dissertations to identify additional papers., Results: After applying inclusion and exclusion criteria to identified hits, this literature search retrieved six papers. Overall findings point towards a beneficial role of lifestyle interventions on mood, weight, blood pressure, lipid profile, physical activity and overall wellbeing. Methodological limitations include small sample size, gender ratio imbalance, inconsistencies in terms of laboratory measures, and lack of randomized controlled trials and absence of follow-up and longitudinal studies to determine the benefits of these factors on clinical and functional outcomes over time, Conclusions: Lifestyle interventions in BD targeting nutrition, exercise, wellbeing alongside beliefs, coping strategies and attitudes towards health show promise in reducing the risk of comorbid ailments in BD. There is still a strong need for studies a) developing interventions which are informed by the patient's input and b) examining the effectiveness of such interventions targeting general wellness using well-controlled trials., (Published by Elsevier Ltd.)

Background: The identification of functional outcome predictors after acute episodes of bipolar disorders (BD) may allow designing appropriate treatment aiming at restoring psychosocial functioning. Our objective was to identify the best functional outcome predictors at a 6-month follow-up after an index manic episode., Methods: We conducted a naturalistic trial (MANACOR) focusing on the global burden of BD, with special emphasis on manic episode-associated costs. We observed patients with BD seen in services of four hospitals in Catalonia (Spain).The total sample included 169 patients with chronic DSM-IV-TR BD I suffering from an acute manic episode who were followed-up for 6 months. In this subanalysis we report the results of a stepwise multiple regression conducted by entering in the model those clinical and sociodemographic variables that were identified through preliminary bivariate Pearson correlations and using total scores on the Functioning Assessment Short Test (FAST) at the 6-month follow-up as the dependent variable., Results: Number of previous depressive episodes (Beta=3.25; t=3.23; p=0.002), presence of psychotic symptoms during the manic index episode (Beta=7.007; t=2.2; p=0.031) and the Body Mass Index (BMI) at baseline (Beta=0.62; t=2.09; p=0.041) were best predictors of functional outcome after a manic episode., Limitations: The main limitations of this study include the retrospective assessment of the episodes, which can be a source of bias, and the 6-month follow-up might have been too short for assessing the course of a chronic illness., Conclusions: Psychotic symptoms at index episode, number of past depressive episodes, and BMI predict worse outcome after 6 months follow-up after a manic episode, and may constitute the target of specific treatment strategies., (Copyright © 2015 Elsevier B.V. All rights reserved.)

An increasing number of studies have focused on cognitive insight (i.e. awareness of one's own thinking) in psychotic disorders. However, little is known about the premorbid and pretreatment correlates of cognitive insight in the early course of psychosis. One hundred and three patients experiencing first-episode psychosis (FEP) were assessed shortly after treatment initiation for cognitive insight. Pretreatment and baseline clinical, functional and neurocognitive characteristics were examined. The self-reflectiveness dimension of cognitive insight was independently associated with clinical insight and executive functioning, whereas self-certainty was associated with premorbid IQ, premorbid academic adjustment and clinical insight. The amount of variance explained by the independent variables was small to moderate. Self-reflectiveness and self-certainty have differential pretreatment correlates in FEP and may reflect separate cognitive processes which require targeted interventions., (© 2013 Published by Elsevier Ireland Ltd.)

Background: There is a lack of scientific consensus about cancer comorbidity in people with central nervous system (CNS) disorders. This study assesses the co-occurrence of cancers in patients with CNS disorders, including Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), autism spectrum disorders, Down's syndrome (DS), Huntington's disease (HD), multiple sclerosis (MS), Parkinson's disease (PD) and schizophrenia (SCZ)., Method: Comprehensive search in PubMed/MEDLINE, Scopus and ISI Web of Knowledge of the literature published before March 2013. We identified 51 relevant articles from 2,229 discrete references, 50 of which contained data suitable for quantitative synthesis (577,013 participants). Pooled effect sizes (ES) were calculated using multiple random-effects meta-analyses. Sources of heterogeneity and uncertainty were explored by means of subgroup and sensitivity analyses, respectively., Results: The presence of CNS disorders was associated with a reduced co-occurrence of cancer (ES = 0.92; 95% confidence interval, CI: 0.87-0.98; I(2) = 94.5%). A consistently lower overall co-occurrence of cancer was detected in patients with neurodegenerative disorders (ES = 0.80; 95% CI: 0.75- 0.86; I(2) = 82.8%), and in those with AD (ES = 0.32; 95% CI: 0.22-0.46; I(2) = 0.0%), PD (ES = 0.83; 95% CI: 0.76-0.91; I(2) = 80.0%), MS (ES = 0.91; 95% CI: 0.87-0.95; I(2) = 30.3%) and HD (ES = 0.53; 95% CI: 0.42-0.67; I(2) = 56.4%). Patients with DS had a higher overall co-occurrence of cancer (ES = 1.46; 95% CI: 1.08-1.96; I(2) = 87.9%). No association was observed between cancer and ALS (ES = 0.97; 95% CI: 0.76-1.25; I(2) = 0.0%) or SCZ (ES = 0.98; 95% CI: 0.90-1.07; I(2) = 96.3%). Patients with PD, MS and SCZ showed (a) higher co-occurrence of some specific cancers (e.g. PD with melanoma, MS with brain cancers and SCZ with breast cancer), and (b) lower co-occurrence of other specific cancers (e.g. lung, prostate and colorectal cancers in PD; lung and prostate cancers in MS; and melanoma and prostate cancer in SCZ)., Conclusion: Increased and decreased co-occurrence of cancer in patients with CNS disorders represents an opportunity to discover biological and non-biological connections between these complex disorders.