Orexinergic Receptor Antagonists as a New Therapeutic Target to Overcome Limitations of Current Pharmacological Treatment of Insomnia Disorder.

Insomnia disorder is a common condition that is considered a risk factor for multiple physical and mental disorders, contributing to reduced quality of life and increased healthcare expenditures. Although cognitive behavioral therapy (CBT) is typically recommended as the primary intervention, its accessibility is hindered by limited resources, prompting the prevalent use of pharmacological interventions as the primary treatment in clinical settings. This study reviews the benefits and risks of current pharmacological treatments for insomnia, with special reference to the orexinergic system as a novel therapeutic target for treatment. The prescription of GABAergic mechanism enhancers (benzodiazepine (BZD) and "Z drugs") has shown efficacy in short-term insomnia treatment (less than 4 weeks), however, concerns arise regarding their long-term effectiveness, unfavorable tolerability and safety profiles, including the potential for dependency. Drugs with antihistamine properties, including certain antidepressants and antipsychotics, exhibit short-term efficacy but have documented tolerability limitations, especially in the elderly. The use of melatonin, available in various formulations, lacks comprehensive long-term data. Dual orexin receptor antagonists (DORAs) such as daridorexant, lemborexant, and suvorexant, represent a novel approach to insomnia treatment by inhibiting wakefulness rather than enhancing sedation. As the only DORA approved for insomnia treatment by the European Medicines Agency (EMA) and Food and Drug Administration (FDA), daridorexant has demonstrated sustained efficacy over a 12-month period, improving nocturnal sleep parameters and daytime functionality, with a favorable safety and tolerability profile.

The black hole of the transition process: dropout of care before transition age in adolescents.

Recent evidence confirms the risks of discontinuity of care when young people make a transition from child and adolescent mental health services (CAMHS) to adult mental health services (AMHS), although robust data are still sparse. We aimed to identify when and how patients get lost to care during transition by tracking care pathways and identifying factors which influence dropping out of care during transition. This is a retrospective observational study of 760 patients who reached the transition age boundary within 12 months before transition time and being treated at CAMHS for at least during preceding 18 months. Data were collected at two time points: last visit to CAHMS and first visit to AHMS. Socio-demographic, clinical and service utilization variables on CAMHS treatment were collected. In the 12 months leading up to the transition boundary, 46.8% of subjects (n = 356) withdrew from CAHMS without further contact with AHMS, 9.3% withdrew from CAHMS but were referred to AHMS by other services, 29% were transferred from CAHMS to AHMS, 10% remained at CAHMS and 5% patients were transferred to alternative services. Fifty-six percent of subjects experience cessation of care before the transition age. The risk of dropout increases with shorter contact time in CAMHS, is greater in subjects without pharmacological treatment, and decreases in subjects with psychosis, bipolar disorder, eating disorders, mental retardation, and neurodevelopmental disorders. This study confirms that a large number of people drop out of care as they approach the CAMHS transition and experience discontinuity of care during this critical period.

The prescriber's guide to classic MAO inhibitors (phenelzine, tranylcypromine, isocarboxazid) for treatment-resistant depression.

This article is a clinical guide which discusses the "state-of-the-art" usage of the classic monoamine oxidase inhibitor (MAOI) antidepressants (phenelzine, tranylcypromine, and isocarboxazid) in modern psychiatric practice. The guide is for all clinicians, including those who may not be experienced MAOI prescribers. It discusses indications, drug-drug interactions, side-effect management, and the safety of various augmentation strategies. There is a clear and broad consensus (more than 70 international expert endorsers), based on 6 decades of experience, for the recommendations herein exposited. They are based on empirical evidence and expert opinion-this guide is presented as a new specialist-consensus standard. The guide provides practical clinical advice, and is the basis for the rational use of these drugs, particularly because it improves and updates knowledge, and corrects the various misconceptions that have hitherto been prominent in the literature, partly due to insufficient knowledge of pharmacology. The guide suggests that MAOIs should always be considered in cases of treatment-resistant depression (including those melancholic in nature), and prior to electroconvulsive therapy-while taking into account of patient preference. In selected cases, they may be considered earlier in the treatment algorithm than has previously been customary, and should not be regarded as drugs of last resort; they may prove decisively effective when many other treatments have failed. The guide clarifies key points on the concomitant use of incorrectly proscribed drugs such as methylphenidate and some tricyclic antidepressants. It also illustrates the straightforward "bridging" methods that may be used to transition simply and safely from other antidepressants to MAOIs.

Essential fatty acids and Barratt impulsivity in gambling disorder.

BACKGROUND: Polyunsaturated fatty acids (PUFA) have been long implicated in the etiopathogenesis of mental illnesses, including disorders characterized by high impulsivity. The objective of most of the studies in this field is to determine the effect of omega-3 supplementation on the impulsive symptoms. In contrast, studies analyzing basal PUFA composition in patients with impulsive behaviors are very scarce, results are not yet conclusive, and to date, no publication has specifically evaluated this in gambling disorder. Therefore, the main purpose of this research is to examine the relationship between basal PUFA composition of plasma and erythrocyte membrane and impulsivity in subjects with gambling disorder. METHODS: It is an observational and cross-sectional study. The sample consisted of fifty-five men with gambling disorder, who voluntarily accepted to participate. Basal composition of PUFA in plasma and erythrocyte membrane was assessed by gas chromatography and mass spectrometry. Trait impulsivity was measured by the Barratt Impulsiveness Scale version 11 (BIS-11). RESULTS: Arachidonic acid (AA)/eicosapentaenoic acid (EPA) ratio in the erythrocyte membrane was negatively correlated with total scores in BIS-11. It was also observed that impulsive gamblers had a higher proportion of EPA and a lower value of AA/EPA and AA/docosahexaenoic acid (DHA) ratio in erythrocyte membrane than non-impulsive gamblers. CONCLUSIONS: These results support the hypothesis that alteration of basal PUFA composition exists in disorders characterized by high impulsivity, although the direction of this is still unknown. Unfortunately, the empirical literature on this field is non-existent at the time and we have no direct means to support or refute these outcomes. Further research is needed to determine the relationship between essential fatty acids and disorders characterized by high impulsivity.

Efficacy of prospective pharmacogenetic testing in the treatment of major depressive disorder: results of a randomized, double-blind clinical trial.

BACKGROUND: A 12-week, double-blind, parallel, multi-center randomized controlled trial in 316 adult patients with major depressive disorder (MDD) was conducted to evaluate the effectiveness of pharmacogenetic (PGx) testing for drug therapy guidance. METHODS: Patients with a CGI-S ≥ 4 and requiring antidepressant medication de novo or changes in their medication regime were recruited at 18 Spanish public hospitals, genotyped with a commercial PGx panel (Neuropharmagen®), and randomized to PGx-guided treatment (n = 155) or treatment as usual (TAU, control group, n = 161), using a computer-generated random list that locked or unlocked psychiatrist access to the results of the PGx panel depending on group allocation. The primary endpoint was the proportion of patients achieving a sustained response (Patient Global Impression of Improvement, PGI-I ≤ 2) within the 12-week follow-up. Patients and interviewers collecting the PGI-I ratings were blinded to group allocation. Between-group differences were evaluated using χ2-test or t-test, as per data type. RESULTS: Two hundred eighty patients were available for analysis at the end of the 12-week follow-up (PGx n = 136, TAU n = 144). A difference in sustained response within the study period (primary outcome) was not observed (38.5% vs 34.4%, p = 0.4735; OR = 1.19 [95%CI 0.74-1.92]), but the PGx-guided treatment group had a higher responder rate compared to TAU at 12 weeks (47.8% vs 36.1%, p = 0.0476; OR = 1.62 [95%CI 1.00-2.61]), and this difference increased after removing subjects in the PGx-guided group when clinicians explicitly reported not to follow the test recommendations (51.3% vs 36.1%, p = 0.0135; OR = 1.86 [95%CI 1.13-3.05]). Effects were more consistent in patients with 1-3 failed drug trials. In subjects reporting side effects burden at baseline, odds of achieving a better tolerability (Frequency, Intensity and Burden of Side Effects Rating Burden subscore ≤2) were higher in the PGx-guided group than in controls at 6 weeks and maintained at 12 weeks (68.5% vs 51.4%, p = 0.0260; OR = 2.06 [95%CI 1.09-3.89]). CONCLUSIONS: PGx-guided treatment resulted in significant improvement of MDD patient's response at 12 weeks, dependent on the number of previously failed medication trials, but not on sustained response during the study period. Burden of side effects was also significantly reduced. TRIAL REGISTRATION: European Clinical Trials Database 2013-002228-18 , registration date September 16, 2013; ClinicalTrials.gov NCT02529462 , retrospectively registered: August 19, 2015.

A Pharmacovigilance Study in First Episode of Psychosis: Psychopharmacological Interventions and Safety Profiles in the PEPs Project.

BACKGROUND: The characterization of the first episode of psychosis and how it should be treated are principal issues in actual research. Realistic, naturalistic studies are necessary to represent the entire population of first episode of psychosis attended in daily practice. METHODS: Sixteen participating centers from the PEPs project recruited 335 first episode of psychosis patients, aged 7 to 35 years. This article describes and discusses the psychopharmacological interventions and safety profiles at baseline and during a 60-day pharmacovigilance period. RESULTS: The majority of first episode of psychosis patients received a second-generation antipsychotic (96.3%), orally (95%), and in adjusted doses according to the product specifications (87.2%). A total of 24% were receiving an antipsychotic polytherapy pattern at baseline, frequently associated with lower or higher doses of antipsychotics than the recommended ones. Eight patients were taking clozapine, all in monotherapy. Males received higher doses of antipsychotic (P=.043). A total of 5.2% of the patients were being treated with long-acting injectable antipsychotics; 12.2% of the patients received anticholinergic drugs, 12.2% antidepressants, and 13.7% mood stabilizers, while almost 40% received benzodiazepines; and 35.52% reported at least one adverse drug reaction during the pharmacovigilance period, more frequently associated with higher antipsychotic doses and antipsychotic polytherapy (85.2% vs 45.5%, P<.001). CONCLUSIONS: These data indicate that the overall pharmacologic prescription for treating a first episode of psychosis in Spain follows the clinical practice guideline recommendations, and, together with security issues, support future research of determinate pharmacological strategies for the treatment of early phases of psychosis, such as the role of clozapine, long-acting injectable antipsychotics, antipsychotic combination, and the use of benzodiazepines.

Relationship between olfactory function and social cognition in euthymic bipolar patients.

OBJECTIVE/INTRODUCTION: There is a close functional and neuroanatomical relationship between olfactory ability and emotional processing. The present study seeks to explore the association between olfactory ability and social cognition, especially facial emotion perception, in euthymic bipolar patients. METHODS: Thirty-nine euthymic outpatients meeting DSM-IV-TR criteria for bipolar disorder and 40 healthy volunteers matched on socio-demographic criteria were recruited. Both groups were assessed at one time point with the University of Pennsylvania Smell Identification Test (UPSIT), the Emotion Recognition Test, and The Faux Pas Recognition Test, as well as measures of general cognition and functioning. RESULTS: The bipolar patients showed a significant impairment in olfactory identification (UPSIT) and social cognition measures compared to healthy controls. Analyses revealed significant relationships between olfactory identification and facial emotion recognition, theory of mind, general cognition, and a trend-level relationship with functioning. Controlling for age and cigarettes smoked, relationships remained significant between olfactory function and facial emotion recognition. CONCLUSION: There is a deficit of olfactory identification in euthymic patients with bipolar disorder that is correlated with a deficit in both verbal and non-verbal measures of social cognition.

Regulating gambling to prevent addiction: more necessary now than ever. / Regular el juego para prevenir la adicción: hoy más necesario que nunca.

The American Psychiatric Association published the 5th Edition of DSM in May 2013, in which the gambling disorder is included within the category of addictive disorders -a long-standing and recurrent demand from the clinical, social and scientific fields. Nevertheless, the harmful effects of gambling have not been considered by the Government, which is the main area of addiction prevention.The present article is a proposal for the regulation of gambling by the Government through the different levels of the State (national, regional and even local), which has the ultimate goal of preventing gambling addiction. This proposal has been presented to the Chamber of Deputies of the Congress, as part of the Congress-Senate Joint Committee for the Study of Drug Problems. The proposed regulation is based on the evidence provided by scientific studies on the prevention of addiction.

En mayo de 2013 apareció la quinta edición de la clasificación de los trastornos mentales (DSM-5) de la American Psychiatric Association (APA, 2013), en la cual se incluye el trastorno de juego dentro de la categoría de trastornos adictivos, que es algo que era demandado desde hace décadas desde los ámbitos clínicos, sociales y científicos. El juego de azar, que según la propia APA tiene la misma consideración que las drogas o el alcohol en cuanto a la activación de los circuitos cerebrales de recompensa y a las consecuencias clínicas del trastorno del juego, no tiene, sin embargo, esa consideración desde el principal ámbito desde donde se debe llevar a cabo la prevención de la adicción, que es en los poderes públicos.El trabajo que presentamos es una propuesta de regulación del juego para llevar a cabo desde la Administración mediante acciones de gobierno que competen a diferentes niveles de la misma (estatal, autonómico e incluso local), con el objetivo final de  prevenir la adicción al juego. Dicha propuesta ha sido presentada tanto a la Dirección General de Ordenación del Juego como a la Cámara del Congreso de los Diputados, esta última en el marco de la Comisión Mixta Congreso-Senado para el Estudio del Problema de las Drogas. En este trabajo se defiende la propuesta de regulación desde la evidencia que proporcionan los estudios científicos en materia de prevención de las adicciones.

Why is it (also) so difficult to legislate gambling in Spain? 'Déjà vu' of what occurred with alcohol. / ¿Por qué (también) es tan difícil legislar sobre juego en España? Un 'déjà vu' de lo ocurrido con el alcohol.

Editorial of vol 28-4.

Editorial del vol 28-4.

Efficacy of cognitive rehabilitation on psychosocial functioning in Borderline Personality Disorder: a randomized controlled trial.

BACKGROUND: Follow-up studies revealed that subjects with borderline personality disorder (BPD) present high rates of clinical remission, although psychosocial functioning often remains impaired. The aim of this study is to evaluate the efficacy of a cognitive rehabilitation intervention versus a psychoeducational program on psychosocial functioning in subjects with BPD. METHODS: A multicenter, randomized, and positive-controlled clinical trial was conducted. Seventy outpatients with BPD were randomized to cognitive rehabilitation or psychoeducational group interventions. Participants were evaluated after completion of the intervention period (16 weeks) and after the follow-up period (6 months). Psychosocial functioning, clinical and neuropsychological outcomes were evaluated. RESULTS: No main effects of group or group x time were observed on functionality but a significant effect of time was found. Post-hoc analyses showed that only cognitive rehabilitation increased psychosocial functioning significantly at endpoint. Psychoeducation showed a significant enhancement of depressive symptoms. CONCLUSIONS: Cognitive rehabilitation and psychoeducational interventions appeared to show good efficacy in improving disabilities in daily life in subjects with BPD. These interventions are easily implemented in mental health settings and have the advantage of improving general functioning and clinical symptoms. TRIAL REGISTRATION: Clinicaltrials.gov: NCT02033044. Registered 9 January 2014.

Antipsychotic switching in bipolar disorders: a systematic review.

With the increasingly widespread use of antipsychotics in bipolar disorder (BD), switching among these agents and between antipsychotics and mood stabilizers has become more common, in particular, since the introduction of the novel atypical antipsychotics with mood stabilizer properties. This systematic review aims to provide a comprehensive update of the current literature in BD about the switching of antipsychotics, among them and between them and mood stabilizers, in acute and maintenance treatment. We conducted a comprehensive, computerized literature search using terms related to antipsychotic switching in BD in the PubMed/Medline, PsycINFO, CINAHL database; the Cochrane Library and; the Clinicaltrials.gov web up to January 9th, 2013 according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. The search returned 4160 articles. After excluding duplications, reviews, case reports and studies that did not fulfil the selection criteria, 8 studies were included. Not only have few articles on antipsychotic switching been published but also recruitment in most studies included mixed samples of patients. In general, antipsychotic switching, regardless of the route of drug administration, was well tolerated and no interference was shown in antipsychotic effectiveness during the interchange of drugs. Metabolic improvement was perceived when the switch involved antipsychotics with a low metabolic risk profile. The evidence-base for antipsychotic switching in BD is scant, and little controlled data is available. Switch from quetiapine to lithium and from risperidone to olanzapine has proven successful. Switching to antipsychotics with low metabolic risk had some positive impact on several safety measures. In stabilized patients, the plateau cross-taper switch may be preferred.

Putative association between the -1415 T/C polymorphism of spermidine/spermine N1-acetyltransferase (SSAT1) gene and alcohol use disorders in women and men.

BACKGROUND: The activity of N-methyl-D-aspartate (NMDA) glutamate receptor, which responds to the levels of polyamines, modifies the neurotoxicity caused by ethanol. We aimed to investigate if the functionality of the spermidine/spermine N1-acetyltransferase (SSAT1) gene could be associated with a differential risk for alcoholism. METHODS: We studied a sample of 586 subjects: 104 alcohol-dependent patients, 273 patients with psychiatric disorders but without substance dependence, and 209 healthy controls. After gender stratification, the allele frequency distribution of the SSAT1 gene was compared between these three groups. RESULTS: In females, the TC genotype was significantly more frequent in alcohol-dependent patients than in non-alcohol-dependent psychiatric controls (χ(2 )= 7.509 df = 2, p = 0.023). A trend was found when alcohol-dependent females were compared with the healthy control group (χ(2 )= 4.897 df = 2, p = 0.086). No statistical differences were found among the males. DISCUSSION AND CONCLUSION: Gender differences in the regulation of SSAT1 gene expression may possibly be due to gender-specific effects of stress, ethanol toxicity, and/or polyamines levels. Further studies are needed to confirm our findings.

Exploration of cannabis use and polygenic risk scores on the psychotic symptom progression of a FEP cohort.

Cannabis use is highly prevalent in first-episode psychosis (FEP) and plays a critical role in its onset and prognosis, but the genetic underpinnings promoting both conditions are poorly understood. Current treatment strategies for cannabis cessation in FEP are clearly inefficacious. Here, we aimed to characterize the association between cannabis-related polygenic risk scores (PRS) on cannabis use and clinical course after a FEP. A cohort of 249 FEP individuals were evaluated during 12 months. Symptom severity was measured with the Positive and Negative Severity Scale and cannabis use with the EuropASI scale. Individual PRS for lifetime cannabis initiation (PRSCI) and cannabis use disorder (PRSCUD) were constructed. Current cannabis use was associated with increased positive symptoms. Cannabis initiation at younger ages conditioned the 12-month symptom progression. FEP patients with higher cannabis PRSCUD reported increased baseline cannabis use. PRSCI was associated with the course of negative and general symptomatology over follow-up. Cannabis use and symptom progression after a FEP were modulated by cannabis PRS, suggesting that lifetime initiation and use disorders may have partially independent genetic factors. These exploratory results may be the first step to identify those FEP patients more vulnerable to cannabis use and worse outcomes to ultimately develop tailored treatments.

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.

Age of first suicide attempt in men and women: an admixture analysis.

OBJECTIVES: To define different subgroups of suicide attempters according to age at onset of suicide attempts. METHODS: Participants were 229 suicide attempters (147 females; 82 males) admitted to a general hospital in Madrid, Spain. We used admixture analysis to determine the best-fitting model for the age at onset of suicide attempts separated by sex. RESULTS: The best fitted model for the age at onset of suicide attempts was a mixture of two gaussian distributions. Females showed an earlier age at onset of suicide attempts in both Gaussian distributions (mean ± S.D.) (26.98 ± 5.69 and 47.98 ± 14.13) than males (32.77 ± 8.11 and 61.31 ± 14.61). Early-onset female attempters were more likely to show borderline personality disorder than late-onset female attempters (OR = 11.11; 95% CI = 2.43-50.0). CONCLUSIONS: Age at onset of suicide attempts characterizes different subpopulations of suicide attempters.

Factors contributing to the utilization of adult mental health services in children and adolescents diagnosed with hyperkinetic disorder.

OBJECTIVES: To examine whether age of First diagnosis, gender, psychiatric comorbidity, and treatment modalities (pharmacotherapy or psychotherapy) at Child and Adolescent Mental Health Services (CAMHS) moderate the risk of Adult Mental Health Services (AMHS) utilization in patients diagnosed with hyperkinetic disorder at CAMHS. METHODS: Data were derived from the Madrid Psychiatric Cumulative Register Study. The target population comprised 32,183 patients who had 3 or more visits at CAMHS. Kaplan-Meier curves were used to assess survival data. A series of logistic regression analyses were performed to study the role of age of diagnosis, gender, psychiatric comorbidity, and treatment modalities. RESULTS: 7.1% of patients presented with hyperkinetic disorder at CAMHS. Compared to preschool children, children and adolescents first diagnosed with hyperkinetic disorder at CAMHS were more likely to use AMHS. Female gender and comorbidity with affective disorders, schizophrenia, schizotypal and delusional disorders increased the risk of use of AMHS. Pharmacological or combined treatment of hyperkinetic disorder diagnosed at CAMHS was associated with increased risk of use at AMHS. CONCLUSIONS: Older age of first diagnosis, female gender, psychiatric comorbidity, and pharmacological treatment at CAMHS are markers of risk for the transition from CAMHS to AMHS in patients with hyperkinetic disorder diagnosed at CAMHS.

Delphi consensus on the physical health of patients with schizophrenia: evaluation of the recommendations of the Spanish Societies of Psychiatry and Biological Psychiatry by a panel of experts.

INTRODUCTION: Available data from scientific literature show that patients with schizophrenia have higher rates of physical comorbidity and excess mortality due to other physical pathologies. The growing interest to investigate and improve the health of these patients has led a group of Spanish experts to publish in 2008 a "Consensus on physical health of patients with schizophrenia from the Spanish Societies of Psychiatry and Biological Psychiatry" (2008 Consensus). These recommendations imply a significant change to the present model of medical attention. OBJECTIVE: To gauge the level of agreement of a group of expert psychiatrists on the clinical criteria and recommendations collected from the scientific literature and the 2008 Consensus on the physical health of patients with schizophrenia. METHOD: The process involved four phases: 1) Scientific Committee established to manage the study and to define the 66-item questionnaire; 2) Panel of 15 experts in psychiatry is established; 3) Submission of questionnaire to the Expert Panel in two consecutive rounds, with an intermediate processing and sharing of results; 4) Evaluation of results, discussion and conclusions between Scientific Committee and Expert Panel. RESULTS: All items, as set by the Scientific Committee and aligned with the recommendations published in the 2008 Consensus, achieved consensus on agreement from the Expert Panel, except 5 items, for which most of the answers were placed in the indeterminate position rate. CONCLUSIONS: The expert criteria shown in this study indicate a global agreement with regard to clinical criteria on the physical health of patients with schizophrenia, as well as with the present recommendations to improve the health of patients having, or at risk to have, other concomitant pathologies. The need to incorporate new intervention guidelines that facilitate a better control and improvement of the physical health of patients with schizophrenia must be disseminated in the psychiatric providers' collectives.

Lack of association between testosterone and suicide attempts.

OBJECTIVE: To determine whether testosterone levels differ in male suicide attempters versus healthy controls and to explore the associations between testosterone levels and time of blood collection, and between testosterone levels and characteristics of suicide attempts. METHOD: A sample of 112 male suicide attempters was studied. Thirty-seven male blood donors were recruited as controls. RESULTS: The mean testosterone levels were 5.1 ± 2.9 ng/ml in male attempters and 4.6 ± 1.6 ng/ml in controls. Group differences in testosterone levels were not significant when we studied the interaction with time of extraction (F = 0.37; d.f. = 2; p = 0.70) or when matched by age and time of extraction (t = -0.74; d.f. = 26; p = 0.47). When partial correlations were performed correcting for the effect of time of extraction, significant partial correlations were found in testosterone levels with history of aggressive behavior and lethality of the attempt. CONCLUSIONS: When circadian variation and age were considered, we found no support for the putative role of testosterone as a biological marker of suicidal behavior. Further research should consider: (1) testosterone and neurosteroids; (2) serial determinations with a minimal time gap between the attempt and the blood extraction; (3) controls within the same time periods, and (4) other variables that may affect testosterone levels, such as body mass index, physical activity and sleep disturbances.

Factors associated with the effectiveness of a telephone-based nursing strategy for enhancing medication adherence in schizophrenia.

A post hoc analysis was made to identify factors associated with success following a 4-month telephone-based strategy for enhancing adherence to antipsychotic treatment in schizophrenia. A total of 928 stable outpatients were randomized to receive a monthly telephone call provided by a nurse or routine clinical care. Logistic regression with a backward stepwise procedure was used. A higher percentage of patients in the intervention group (25.7%, n=109) improved adherence at the end of the study compared with the control group (16.8%, n=74) (p=0.0013). The intervention was significantly associated with adherence improvement in those patients with a previous negative attitude towards medication (OR=4.7, 95% CI =2.4-9.0, p<0.0001). A slight concordance was obtained between adherence improvement and improvement in patient perception of treatment (kappa=0.21; 95% CI=0.15-0.27). The identification of factors related to the effectiveness of a specific intervention would offer clinicians the opportunity to more adequately select patients who are eligible for such intervention.

Identification of EP300 as a Key Gene Involved in Antipsychotic-Induced Metabolic Dysregulation Based on Integrative Bioinformatics Analysis of Multi-Tissue Gene Expression Data.

Antipsychotics (APs) are associated with weight gain and other metabolic abnormalities such as hyperglycemia, dyslipidemia and metabolic syndrome. This translational study aimed to uncover the underlying molecular mechanisms and identify the key genes involved in AP-induced metabolic effects. An integrative gene expression analysis was performed in four different mouse tissues (striatum, liver, pancreas and adipose) after risperidone or olanzapine treatment. The analytical approach combined the identification of the gene co-expression modules related to AP treatment, gene set enrichment analysis and protein-protein interaction network construction. We found several co-expression modules of genes involved in glucose and lipid homeostasis, hormone regulation and other processes related to metabolic impairment. Among these genes, EP300, which encodes an acetyltransferase involved in transcriptional regulation, was identified as the most important hub gene overlapping the networks of both APs. Then, we explored the genetically predicted EP300 expression levels in a cohort of 226 patients with first-episode psychosis who were being treated with APs to further assess the association of this gene with metabolic alterations. The EP300 expression levels were significantly associated with increases in body weight, body mass index, total cholesterol levels, low-density lipoprotein cholesterol levels and triglyceride concentrations after 6 months of AP treatment. Taken together, our analysis identified EP300 as a key gene in AP-induced metabolic abnormalities, indicating that the dysregulation of EP300 function could be important in the development of these side effects. However, more studies are needed to disentangle the role of this gene in the mechanism of action of APs.