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

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

Risk of suicide attempt repetition after an index attempt: A systematic review and meta-analysis.

OBJECTIVES: To estimate the risk of suicide attempt repetition among individuals with an index attempt. It also aims to study the role of risk factors and prevention programme in repetition. METHODS: This systematic review and meta-analysis was conducted in keeping with the PRISMA 2020 guidelines. Studies on attempt repetition (both cohort studies and intervention studies) were searched from inception to 2022. RESULTS: A total of 110 studies comprising 248,829 attempters was reviewed. The overall repetition rate was 0.20 (0.17, 0.22). Repetition risk linearly increased over time. A higher risk of attempt repetition was associated with female sex and index attempts in which self-cutting methods were used. Moreover, a mental disorder diagnosis was associated with an increasing repetition risk (OR = 2.02, p < .01). The delivery of a preventive programme reduced the repetition risk, OR = 0.76, p < .05; however, this effect was significant for psychotherapy interventions, OR = 0.38, p < .01. CONCLUSION: One in five suicide attempters will engage in a new suicide attempt. An elevated repetition risk is associated with being female, more severe index methods and psychiatric disorder diagnosis. Preventive programmes, particularly psychotherapy, may contribute to reducing repetition risk and eventually save lives.

Two-year evaluation of a multifamily psychoeducational program (PROTEC) in the family burden and prognosis of bipolar patients.

INTRODUCTION: Bipolar disorder causes a significant burden on the lives of patients and their families. The family is one of the targets for therapeutic intervention, related to the prognosis in patients with bipolar disorder. AIM: To assess the effectiveness of a multifamily psychoeducational program for people with bipolar disorder, in the family burden: objective and subjective and in the variables related to the course of the patients with bipolar disorder (symptoms, adherence, functionality, hospitalizations), comparing it with a control group (CG). MATERIALS AND METHODS: A total of 148 relatives of bipolar patients and 148 bipolar patients were recruited. The sample was randomized (experimental group [EG] and CG) and with single-blind evaluations (baseline, at 5 months and one year). Clinical and sociodemographic variables were collected from families and patients (family burden self-report scale, Strauss-Carpenter Scale, Global Assessment of Functioning, Morisky Green adherence Scale). Both, EG and CG received 8 multifamily sessions, applied exclusively on the relatives of patients with bipolar disorder, but in the EG a psychoeducational treatment was carried out and in the CG only playful and current topics were discussed. Bivariate and logistic regression models were used, among others. RESULTS: The caregivers and patients of the EG and CG did not differ in any of the baseline variables (sociodemographic and clinical) (P>.001). In the total sample, the baseline objective burden was light (mean 0.6±0.4) and the subjective ones was medium-moderate (mean 1.1±0.3). During the follow-up, in relation to the variables of the caregivers, there was a greater reduction in the objective burden in the EG compared to the CG (5 months P=.006; one year P=.002). It was found that the objective burden (P=.006) and the subjective burden (P=.003) were significantly reduced over a year in EG but not in the CG. During the follow-up, the patients whose caregivers belonged to the EG showed a greater increase in the frequency of social activity (P=.008), in the work activity (P=.002), and global functioning (P=.002), and reduced their symptoms (P≤.001). Longitudinal analyses, over a year, showed that patients in the EG had a greater improvement in functionality compared to patients in the CG (P=.001). After the intervention, adherence to pharmacological treatment improved more in EG than in the CG (P≤.001). Regarding hospitalizations, any patients in the CG were hospitalized during the 5 months after the intervention, while 27.8% of the patients in the CG were hospitalized (P≤.001); the difference between groups remained significant in the long term (one year: P≤.001; 2 years: P≤.001). There were no significant differences between groups in the pharmacological treatment of the patients in any of the evaluations. CONCLUSIONS: The multifamily psychoeducational intervention group improved the family burden after the intervention. Likewise, bipolar patients, whose families attended the EG, improved significantly, over a year, the functionality, the frequency of social contacts, the work status, the adherence to treatment, and reduced their symptoms. In addition, in the EG, the percentage of hospitalizations during the 2 years of follow-up was significantly reduced.

Clinical predictors and psychosocial risk factors of suicide attempt severity.

BACKGROUND: Suicide attempts are an important predictor of completed suicide and may differ in terms of severity of medical consequences or medical lethality. There is little evidence on serious suicide attempt (SSA) and very few studies have compared SSA with non-SSA. OBJECTIVE: The aim of this multisite, coordinated, cohort study was to analyze the role of clinical variables and the sociodemographic and psychological risk factors of SSA. METHOD: In this multisite, coordinated, cohort study, 684 participants (222 for the mild suicide attempt group, 371 for the moderate suicide attempt group and 91 for the SSA group) were included in the study. Ordinal regression models were performed to analyze the predictor variables of SSA. RESULTS: Early physical abuse (OR=1.231) and impulsivity (OR=1.036) were predictors of SSA, while depressive symptoms were associated with a lower risk of SSA. CONCLUSION: Environmental and psychological factors as physical abuse and impulsivity are related with severe suicide severity. These findings will help to develop strategies to prevent suicide and may be considered for the treatment and management of suicide.

Relapse of first-episode schizophrenia patients and neurocognitive impairment: The role of dopaminergic and anticholinergic burden.

BACKGROUND: The prevention of relapse may be a key factor to diminish the cognitive impairment of first-episode schizophrenia (FES) patients. We aimed to ascertain the effects of relapse, and dopaminergic and anticholinergic treatment burdens on cognitive functioning in the follow-up. METHODS: Ninety-nine FES patients participated in this study. Cognitive assessments were performed at baseline and after 3 years of follow-up or, in those patients who relapsed, after >2 months of stabilization of the new acute psychotic episode. The primary outcomes were final cognitive dimensions. RESULTS: Repeated measures MANOVA analyses showed improvements in the whole sample on the end-point assessments in processing speed and social cognition. However, only impairment in social cognition showed a significant interaction with relapse by time in this sample. Relapse in FES patients was significantly associated with poor performance on end-point assessments of working memory, social cognition and global cognitive score. Anticholinergic burden, but not dopaminergic burden, was associated with verbal memory impairment. These significant associations resulted after controlling for baseline cognitive functioning, relapse and dopaminergic burden. CONCLUSIONS: The relationship between relapse and cognitive impairment in recovered FES patients seems to be particularly complex at the short-term follow-up of these patients. While relapse was associated with working memory, social cognition impairments and global cognitive score, anticholinergic burden might play an additional worsening effect on verbal memory. Thus, tailoring or changing antipsychotics and other drugs to reduce their anticholinergic burden may be a potential modifiable factor to diminish cognitive impairment at this stage of the illness.

Cognitive Behavioral Therapy Program for Cannabis Use Cessation in First-Episode Psychosis Patients: A 1-Year Randomized Controlled Trial.

Despite the negative influence of cannabis use on the development and prognosis of first-episode psychosis (FEP), there is little evidence on effective specific interventions for cannabis use cessation in FEP. The aim of this study was to compare the efficacy of a specific cognitive behavioral therapy (CBT) for cannabis cessation (CBT-CC) with treatment as usual (TAU) in FEP cannabis users. In this single-blind, 1-year randomized controlled trial, 65 participants were randomly assigned to CBT-CC or TAU. The primary outcome was the reduction in cannabis use severity. The CBT-CC group had a greater decrease in cannabis use severity and positive psychotic symptoms over time, and a greater improvement in functioning at post-treatment than TAU. The treatment response was also faster in the CBT-CC group, reducing cannabis use, anxiety, positive and general psychotic symptoms, and improving functioning earlier than TAU in the follow-up. Moreover, patients who stopped and/or reduced cannabis use during the follow-up, decreased psychotic symptoms and increased awareness of disease compared to those who continued using cannabis. Early intervention based on a specific CBT for cannabis cessation, may be effective in reducing cannabis use severity, in addition to improving clinical and functional outcomes of FEP cannabis users.

Inflammation biomarkers in suicide attempts and their relation to abuse, global functioning and cognition.

OBJECTIVES: To explore the link between cytokines and suicide attempts and their relationship with the psychological aspects of this complex multifactorial phenomenon. METHODS: 96 participants, including 20 patients with a recent suicide attempt and diagnosis of Major Depression Disorder (MDD), 33 MDD patients with a lifetime history of suicide attempt, 23 non-attempter MDD patients, and 20 healthy controls underwent an assessment on depressive symptoms, global functioning, aggressive behaviour, presence of abuse and attention performance. Additionally, all participants had a blood extraction for IL-2, IL2-R, IL-4, IL-6, and TNF-α plasma levels analysis. RESULTS: IL-6 levels were significantly different across groups (F(3,89)=3.690; p = 0.015), with higher concentrations in both recent (p = 0.04) and distant (p = 0.015) attempt in comparison to MDD non-attempters. IL-6 was associated with adult physical abuse (B = 2.591; p = 0.021), lower global functioning score (B = -0.512; p = 0.011), and poorer performance on attention (B = -0.897; p = 0.011). CONCLUSIONS: Recent and distant suicidal behaviour is associated with elevated IL-6 levels, which may be influenced by stressful and traumatic experiences. Elevated concentrations of IL-6 could have a negative impact on attention, increasing suicide risk. More research is needed to clarify the role of cytokines in suicide-related features to explore novel treatments and more effective preventive interventions.

Cognition in Recent Suicide Attempts: Altered Executive Function.

Background: Neuropsychological alterations can lead to inaccurate perception, interpretation, and response to environmental information, which could be a risk factor for suicide. Methods: Ninety-six subjects were recruited from the Psychiatry Department of the Araba University Hospital-Santiago, including 20 patients with a recent attempt and diagnosis of major depressive disorder (MDD) according to DSM-V, 33 MDD patients with history of attempted suicide, 23 non-attempter MDD patients, and 20 healthy controls. All participants underwent a clinical interview and neuropsychological assessment on the following cognitive domains: working memory, processing speed, decision-making, executive function, and attention. Backward multiple regressions were performed adjusting for significant confounding variables. For group comparisons, ANOVA and Bonferroni post-hoc tests were performed with a p < 0.05 significance level. Results: The patient groups did not differ regarding severity of depression and stressful events in the last 6 months. In comparison to healthy controls, depressed patients with lifetime suicide attempts had more general trauma (p = 0.003), emotional abuse (p = 0.003), emotional negligence (p = 0.006), and physical negligence (p = 0.009), and depressed patients with recent suicide attempts had experienced more child sexual abuse (p = 0.038). Regarding neuropsychological assessment, all patient groups performed significantly worse than did healthy controls in processing speed, decision-making, and attention. Comparisons between patient groups indicated that recent suicide attempters had poorer performance on executive function in comparison to both depressed lifetime attempters and depressed non-attempters (B = 0.296, p = 0.019, and B = 0.301, p = 0.028, respectively). Besides, women with recent attempts had slightly better scores on executive function than males. Regarding the rest of the cognitive domains, there were no significant differences between groups. Conclusion: Executive function performance is altered in recent suicide attempts. As impaired executive function can be risk factor for suicide, preventive interventions on suicide should focus on its assessment and rehabilitation.

A Multicentre, Randomised, Controlled Trial of a Combined Clinical Treatment for First-Episode Psychosis.

INTRODUCTION: There is evidence that early intervention contributes to improving the prognosis and course of first-episode psychosis (FEP). However, further randomised treatment clinical trials are needed. OBJECTIVES: The aim of this study was to compare the efficacy of a combined clinical treatment involving Cognitive Behavioural Therapy (CBT) as an adjunctive to treatment-as-usual (TAU) (CBT+TAU) versus TAU alone for FEP. PATIENTS AND METHODS: In this multicentre, single-blind, randomised controlled trial, 177 participants were randomly allocated to either CBT+TAU or TAU. The primary outcome was post-treatment patient functioning. RESULTS: The CBT+TAU group showed a greater improvement in functioning, which was measured using the Global Assessment Functioning (GAF) and Functioning Assessment Short Test (FAST), compared to the TAU group post-treatment. The CBT+TAU participants exhibited a greater decline in depressive, negative, and general psychotic symptoms; a better awareness of the disease and treatment adherence; and a greater increase in brain-derived neurotrophic factor levels than TAU participants. CONCLUSIONS: Early intervention based on a combined clinical treatment involving CBT as an adjunctive to standard treatment may improve clinical and functional outcomes in FEP.

A systematic review of sex-based differences in effectiveness and adverse effects of clozapine.

Clozapine is one of the most widely used antipsychotics for treating psychiatric illnesses such as schizophrenia and bipolar disorder. This drug, however, is associated with adverse effects such as weight gain, metabolic syndrome, and blood dyscrasias. The manifestations of mental illness may differ between men and women. Yet, there is little evidence on the influence of sex on treatment response or the occurrence of AEs. To fill this gap of knowledge, we carried out a systematic review of the literature on sex differences in the effectiveness and adverse effects of clozapine. Scant evidence has been published on differences in effectiveness of clozapine between men and women. Indeed, to the best of our knowledge, this issue has only been addressed in a published study. Regarding adverse effects, males have been reported to be more likely to develop metabolic abnormalities such as cholesterol or triglycerides, hypertension, and cardiovascular risk, while females are at a higher risk for gaining weight, developing diabetes, and needing laxatives. Nevertheless, given the scarcity of sex-based studies on this drug, further studies are needed to explore sex-based differences, as the results obtained may be crucial to clinical practice and help improve the quality of life of patients.

Influencia del sexo en el tratamiento con olanzapina: una revisión sistemática / Gender differences in olanzapine treatment: A systematic review

La olanzapina es un antipsicótico comúnmente utilizado como tratamiento de enfermedades como la esquizofrenia y el trastorno bipolar. En ocasiones la manifestación de la enfermedad difiere entre sexos, pero poco se ha investigado sobre la influencia de esta diferencia biológica en la respuesta al tratamiento o en los efectos secundarios. En esta revisión sistemática analizamos estas diferencias de sexo en la efectividad y en los efectos adversos de la olanzapina. Aunque algunos estudios mostraron mayor efectividad en mujeres, este resultado es ambiguo al no encontrar diferencias en otros trabajos. Por otro lado, encontramos mayor tendencia de los hombres a la ganancia de peso y al parkinsonismo, mientras que más mujeres experimentaron mareos, mayor aumento del colesterol y del intervalo QT. Dado el amplio uso a nivel mundial de la olanzapina, es importante realizar futuros estudios analizando las diferencias observadas, ya que podrían ser cruciales para mejorar la calidad de vida de los pacientes

Olanzapine is an antipsychotic drug commonly used in the treatment of illnesses such as schizophrenia and bipolar disorder. Occasionally the manifestation of the illness differs between genders, but little has been investigated on the influence of this biological difference in the response to the treatment or the secondary effects. In this systematic review, an analysis is made of these gender differences on the effectiveness and adverse effects of olanzapine treatment. Although some studies showed a higher effectiveness in women, this was ambiguous due to not finding any differences in other works. On the other hand, there was a greater tendency for men to gain weight and suffer from Parkinson symptoms, while the women were more likely to suffer from dizzy spells, a greater increase in cholesterol, and in QT interval. Given the worldwide use of olanzapine, it is important that further studies should be performed to analyse these differences observed, since they could be crucial for improving the quality of life of the patients

White Matter Tract Integrity in Alzheimer's Disease vs. Late Onset Bipolar Disorder and Its Correlation with Systemic Inflammation and Oxidative Stress Biomarkers.

Background: Late Onset Bipolar Disorder (LOBD) is the development of Bipolar Disorder (BD) at an age above 50 years old. It is often difficult to differentiate from other aging dementias, such as Alzheimer's Disease (AD), because they share cognitive and behavioral impairment symptoms. Objectives: We look for WM tract voxel clusters showing significant differences when comparing of AD vs. LOBD, and its correlations with systemic blood plasma biomarkers (inflammatory, neurotrophic factors, and oxidative stress). Materials: A sample of healthy controls (HC) (n = 19), AD patients (n = 35), and LOBD patients (n = 24) was recruited at the Alava University Hospital. Blood plasma samples were obtained at recruitment time and analyzed to extract the inflammatory, oxidative stress, and neurotrophic factors. Several modalities of MRI were acquired for each subject, Methods: Fractional anisotropy (FA) coefficients are obtained from diffusion weighted imaging (DWI). Tract based spatial statistics (TBSS) finds FA skeleton clusters of WM tract voxels showing significant differences for all possible contrasts between HC, AD, and LOBD. An ANOVA F-test over all contrasts is carried out. Results of F-test are used to mask TBSS detected clusters for the AD > LOBD and LOBD > AD contrast to select the image clusters used for correlation analysis. Finally, Pearson's correlation coefficients between FA values at cluster sites and systemic blood plasma biomarker values are computed. Results: The TBSS contrasts with by ANOVA F-test has identified strongly significant clusters in the forceps minor, inferior longitudinal fasciculus, inferior fronto-occipital fasciculus, and cingulum gyrus. The correlation analysis of these tract clusters found strong negative correlation of AD with the nerve growth factor (NGF) and brain derived neurotrophic factor (BDNF) blood biomarkers. Negative correlation of AD and positive correlation of LOBD with inflammation biomarker IL6 was also found. Conclusion: TBSS voxel clusters tract atlas localizations are consistent with greater behavioral impairment and mood disorders in LOBD than in AD. Correlation analysis confirms that neurotrophic factors (i.e., NGF, BDNF) play a great role in AD while are absent in LOBD pathophysiology. Also, correlation results of IL1 and IL6 suggest stronger inflammatory effects in LOBD than in AD.

Online psycho-education to the treatment of bipolar disorder: protocol of a randomized controlled trial.

BACKGROUND: Bipolar disorder patients frequently present recurrent episodes and often experience subsyndromal symptoms, cognitive impairment and difficulties in functioning, with a low quality of life, illness relapses and recurrent hospitalization. Early diagnosis and appropriate intervention may play a role in preventing neuroprogression in this disorder. New technologies represent an opportunity to develop standardized psychological treatments using internet-based tools that overcome some of the limitations of face-to-face treatments, in that they are readily accessible and the timing of therapy can be tailored to user needs and availability. However, although many psychological programs are offered through the web and mobile devices for bipolar disorder, there is a lack of high quality evidence concerning their efficacy and effectiveness due to the great variability in measures and methodology used. METHODS: This clinical trial is a simple-blind randomized trial within a European project to compare an internet-based intervention with treatment as usual. Bipolar disorder patients are to be included and randomly assigned to one of two groups: 1) the experimental group (tele-care support) and 2) the control group. Participants in both groups will be evaluated at baseline (pre-treatment) and post-treatment. DISCUSSION: This study describes the design of a clinical trial based on psychoeducation intervention that may have a significant impact on both prognosis and treatment in bipolar disorder. Specifically, bringing different services together (service aggregation), it is hoped that the approach proposed will significantly increase the impact of information and communication technologies on access and adherence to treatment, quality of the service, patient safety, patient and professional satisfaction, and quality of life of patients. TRIAL REGISTRATION: NCT02924415 . Retrospectively registered 27 September 2016.

Psychometric properties and validation of a four-item version of the Strauss-Carpenter scale in bipolar disorder.

BACKGROUND: Bipolar disorder is a chronic illness that impairs functioning and affects the quality of life of patients. The onset of this illness usually occurs at an early age, and the risk of relapse remains high for decades. Thus, due to the great clinical relevance of identifying long-term predictors of functioning in bipolar disorder, Strauss and Carpenter developed a scale composed of items known to have prognostic value. METHODS: To determine the clinical usefulness of the four-item Strauss-Carpenter scale in bipolar disorder, a 1-year prospective follow-up study was carried out. The internal consistency, convergent and discriminant validity, and test-retest reliability of the scale were assessed. We also compared the Strauss-Carpenter scale with the reference scales Global Assessment Functioning (GAF), Clinical Global Impression for Bipolar Disorder, the Modified Version (CGI-BIP-M) and the Sheehan Disability Scale (Sheehan). Additionally, a cut-off point for remission was established. RESULTS: The total sample was composed of 98 patients with a diagnosis of bipolar disorder. The four-item version of the Strauss-Carpenter scale showed to have appropriate psychometric properties, comparable to those of reference scales. The best cut-off point for remission was 14. CONCLUSIONS: The four-item version of the Strauss-Carpenter scale has suitable validity and reliability for the assessment of functioning in patients with bipolar disorder.

Opposite Cannabis-Cognition Associations in Psychotic Patients Depending on Family History.

The objective of this study is to investigate cognitive performance in a first-episode psychosis sample, when stratifying the interaction by cannabis use and familial or non-familial psychosis. Hierarchical-regression models were used to analyse this association in a sample of 268 first-episode psychosis patients and 237 controls. We found that cannabis use was associated with worse working memory, regardless of family history. However, cannabis use was clearly associated with worse cognitive performance in patients with no family history of psychosis, in cognitive domains including verbal memory, executive function and global cognitive index, whereas cannabis users with a family history of psychosis performed better in these domains. The main finding of the study is that there is an interaction between cannabis use and a family history of psychosis in the areas of verbal memory, executive function and global cognition: that is, cannabis use is associated with a better performance in patients with a family history of psychosis and a worse performance in those with no family history of psychosis. In order to confirm this hypothesis, future research should explore the actual expression of the endocannabinoid system in patients with and without a family history of psychosis.

Cognitive behavioral therapy program for cannabis use cessation in first-episode psychosis patients: study protocol for a randomized controlled trial.

BACKGROUND: The high rate of cannabis use among patients with first-episode psychosis (FEP), as well as the associated negative impact on illness course and treatment outcomes, underlines the need for effective interventions in these populations. However, to date, there have been few clinical treatment trials (of pharmacological or psychological interventions) that have specifically focused on addressing comorbid cannabis use among these patients. The aim of this paper is to describe the design of a study protocol for a randomized controlled trial in which the objective is to assess the efficacy of a specific cognitive behavioral therapy program for cannabis cessation in patients with FEP compared to standard treatment (psychoeducation). METHODS/DESIGN: This is a single-blind randomized study with 1 year of follow-up. Patients are to be randomly assigned to one of two treatments: (1) specific cognitive behavioral therapy for cannabis cessation composed of 1-hour sessions once a week for 16 weeks, in addition to pharmacological treatment scheduled by the psychiatrist, or (2) a control group (psychoeducation + pharmacological treatment) following the same format as the experimental group. Participants in both groups will be evaluated at baseline (pre-treatment), at 16 weeks (post-treatment), and at 3 and 6 months and 1 year of follow-up. The primary outcome will be that patients in the experimental group will have greater cannabis cessation than patients in the control group at post-treatment. The secondary outcome will be that the experimental group will have better clinical and functional outcomes than the control group. DISCUSSION: This study provides the description of a clinical trial design based on specific cognitive behavioral therapy for cannabis cessation in FEP patients, aiming to improve clinical and functional outcome, as well as tackling the addictive disorder. TRIAL REGISTRATION: NCT02319746 ClinicalTrials.gov Identifier. ClinicalTrials.gov Protocol and Results Registration System (PRS) Receipt Release Date: 15 December 2014.

Prognostic Value of Affective Symptoms in First-Admission Psychotic Patients.

BACKGROUND: Very little research has been conducted in patients with first-episode psychosis using a dimensional approach. Affective dimensional representations might be useful to predict the clinical course and treatment needs in such patients. METHODS: Weincluded 112 patients with first-episode psychosis in a longitudinal-prospective study with a five-year follow-up (N = 82). Logistic analyses were performed to determine the predictive factors associated with depressive, manic, activation, and dysphoric dimensions. RESULTS: High scores on the depressive dimension were associated with the best prognosis. On the other hand, high scores on the activation dimension and the manic dimension were associated with a poorer prognosis in terms of relapses. Only the dysphoric dimension was not associated with syndromic or functional prognosis. CONCLUSION: Ourresults suggest that the pattern of baseline affective symptoms helps to predict the course of psychotic illness. Therefore, the systematic assessment of affective symptoms would enable us to draw important conclusions regarding patients' prognosis. Interventions for patients with high scores on manic or activation dimensions could be beneficial in decreasing relapses in first-episode psychosis.

Eigenanatomy on Fractional Anisotropy Imaging Provides White Matter Anatomical Features Discriminating Between Alzheimer's Disease and Late Onset Bipolar Disorder.

BACKGROUND: Late Onset Bipolar Disorder (LOBD) is the arousal of Bipolar Disorder (BD) at old age (>60) without any previous history of disorders. LOBD is often difficult to distinguish from degenerative dementias, such as Alzheimer Disease (AD), due to comorbidities and common cognitive symptoms. Moreover, LOBD prevalence is increasing due to population aging. Biomarkers extracted from blood plasma are not discriminant because both pathologies share pathophysiological features related to neuroinflammation, therefore we look for anatomical features highly correlated with blood biomarkers that allow accurate diagnosis prediction. This may shed some light on the basic biological mechanisms leading to one or another disease. Moreover, accurate diagnosis is needed to select the best personalized treatment. OBJECTIVE: We look for white matter features which are correlated with blood plasma biomarkers (inflammatory and neurotrophic) discriminating LOBD from AD. MATERIALS: A sample of healthy controls (HC) (n=19), AD patients (n=35), and BD patients (n=24) has been recruited at the Alava University Hospital. Plasma biomarkers have been obtained at recruitment time. Diffusion weighted (DWI) magnetic resonance imaging (MRI) are obtained for each subject. METHODS: DWI is preprocessed to obtain diffusion tensor imaging (DTI) data, which is reduced to fractional anisotropy (FA) data. In the selection phase, eigenanatomy finds FA eigenvolumes maximally correlated with plasma biomarkers by partial sparse canonical correlation analysis (PSCCAN). In the analysis phase, we take the eigenvolume projection coefficients as the classification features, carrying out cross-validation of support vector machine (SVM) to obtain discrimination power of each biomarker effects. The John Hopkins Universtiy white matter atlas is used to provide anatomical localizations of the detected feature clusters. RESULTS: Classification results show that one specific biomarker of oxidative stress (malondialdehyde MDA) gives the best classification performance ( accuracy 85%, F-score 86%, sensitivity, and specificity 87%, ) in the discrimination of AD and LOBD. Discriminating features appear to be localized in the posterior limb of the internal capsule and superior corona radiata. CONCLUSION: It is feasible to support contrast diagnosis among LOBD and AD by means of predictive classifiers based on eigenanatomy features computed from FA imaging correlated to plasma biomarkers. In addition, white matter eigenanatomy localizations offer some new avenues to assess the differential pathophysiology of LOBD and AD.

Involvement of NRN1 gene in schizophrenia-spectrum and bipolar disorders and its impact on age at onset and cognitive functioning.

OBJECTIVES: Neuritin 1 gene (NRN1) is involved in neurodevelopment processes and synaptic plasticity and its expression is regulated by brain-derived neurotrophic factor (BDNF). We aimed to investigate the association of NRN1 with schizophrenia-spectrum disorders (SSD) and bipolar disorders (BPD), to explore its role in age at onset and cognitive functioning, and to test the epistasis between NRN1 and BDNF. METHODS: The study was developed in a sample of 954 SSD/BPD patients and 668 healthy subjects. Genotyping analyses included 11 SNPs in NRN1 and one functional SNP in BDNF. RESULTS: The frequency of the haplotype C-C (rs645649-rs582262) was significantly increased in patients compared to controls (P = 0.0043), while the haplotype T-C-C-T-C-A (rs3763180-rs10484320-rs4960155-rs9379002-rs9405890-rs1475157) was more frequent in controls (P = 3.1 × 10(-5)). The variability at NRN1 was nominally related to changes in age at onset and to differences in intelligence quotient, in SSD patients. Epistasis between NRN1 and BDNF was significantly associated with the risk for SSD/BPD (P = 0.005). CONCLUSIONS: Results suggest that: (i) NRN1 variability is a shared risk factor for both SSD and BPD, (ii) NRN1 may have a selective impact on age at onset and intelligence in SSD, and (iii) the role of NRN1 seems to be not independent of BDNF.

Subclinical depressive symptoms and continued cannabis use: predictors of negative outcomes in first episode psychosis.

BACKGROUND: Although depressive symptoms in first episode psychosis have been associated with cannabis abuse, their influence on the long-term functional course of FEP patients who abuse cannabis is unknown. The aims of the study were to examine the influence of subclinical depressive symptoms on the long-term outcome in first episode-psychosis patients who were cannabis users and to assess the influence of these subclinical depressive symptoms on the ability to quit cannabis use. METHODS: 64 FEP patients who were cannabis users at baseline were followed-up for 5 years. Two groups were defined: (a) patients with subclinical depressive symptoms at least once during follow-up (DPG), and (b) patients without subclinical depressive symptoms during follow-up (NDPG). Psychotic symptoms were measured using the Positive and Negative Syndrome Scale (PANSS), depressive symptoms using the Hamilton Depression Rating Scale (HDRS)-17, and psychosocial functioning was assessed using the Global Assessment of Functioning (GAF). A linear mixed-effects model was used to analyze the combined influence of cannabis use and subclinical depressive symptomatology on the clinical outcome. RESULTS: Subclinical depressive symptoms were associated with continued abuse of cannabis during follow-up (ß= 4.45; 95% confidence interval [CI]: 1.78 to 11.17; P = .001) and with worse functioning (ß = -5.50; 95% CI: -9.02 to -0.33; P = .009). CONCLUSIONS: Subclinical depressive symptoms and continued cannabis abuse during follow-up could be predictors of negative outcomes in FEP patients.