Genomic, epigenetic and proteomic biomarkers in psychosis: a translational approach including high- risk individuals, patients with schizophrenia and animal models: ERA-NET PROJECT (GEPI-BIOPSY)

Presentación de la segunda jornadaGenomic, epigenetic and proteomic biomarkers in psychosis: a translational approach including high- risk individuals, patients with schizophrenia and animal models ERA-NET PROJECT (GEPI-BIOPSY)N

Religiosity and Psychotic Ideation in Stable Schizophrenia : A Role for Empathic Perspective-Taking

The relationship between religiosity and different components of empathy was explored in schizophrenia patients. A total of 81 stable schizophrenia patients and 95 controls from the nearby community completed self-reported questionnaires assessing religiosity and empathy (through the Interpersonal Reactivity Index, IRI). Patients with schizophrenia showed higher religiousness than controls and they presented less perspective-taking and empathic concern but increased personal distress in IRI scores. Regression analyses unveiled an association between religiosity and perspective-taking in schizophrenics after adjusting for age, gender, and psychotic symptoms. In conclusion, religiosity in patients with schizophrenia may be linked to variations in perspective- taking as a component of empathy

Moderators and mediators of antipsychotic response in delusional disorder : Further steps are needed

Delusional disorder (DD) has been traditionally considered a relatively rare and treatment-resistant psychotic disorder. In the last decade, increasing attention has focused on therapeutic outcomes of individuals affected by this disorder. The aim of this paper is to provide a synthesis of the literature addressing two very important questions arising from DD research: (1) For which patients with DD do antipsychotic medications work best (the moderators of response); and (2) What variables best explain the relationship between such treatments and their effectiveness (the mediators of response). We searched PubMed and Google Scholar databases for English, German, French and Spanish language papers published since 2000. We also included a few classic earlier papers addressing this topic. Variables potentially moderating antipsychotic response in DD are gender, reproductive status, age, duration of illness, the presence of comorbidity (especially psychiatric comorbidity) and its treatment, brain structure, and genetics of neurochemical receptors and drug metabolizing enzymes. Antipsychotic and hormonal blood levels during treatment, as well as functional brain changes, are potential mediating variables. Some, but not all, patients with DD benefit from antipsychotic treatment. Understanding the circumstances under which treatment works best can serve to guide optimal management

Limited Joint Mobility Progression In Type 1 Diabetes: A 15-year Follow-up Study

Objective. To assess the evolution of joint mobility over a period of 15 years in type 1 diabetic patients and healthy controls and to determine whether microalbuminuria is associated with a different evolution of joint mobility. Methods. Joint mobility of hand and wrist was determined in 63 patients with type 1 diabetes and 63 healthy subjects. Fifteen years later, 37 (58.7%) diabetic patients and 16 (25.4%) healthy subjects were studied again. Joint mobility was assessed with the Prayer sign and by measuring the angle of maximal flexion of the fifth and third metacarpophalangeal (MCP) joints and wrist. Patients with diabetes were visited 2-4 times every year with regular assessment of glycated hemoglobin (HbA1(c)), urinary albumin excretion (UAE), and ophthalmoscopy. Results. Fifteen years after the initial exam, diabetic patients showed reduced flexion of the fifth MCP joint (82.6 +/- 5.8 versus 76.0 +/- 6.4 degrees, p < 0 001) and wrist (75.9 +/- 8.1 versus 73.2 +/- 7.4 degrees, p = 0 015) compared to baseline examination. Joint mobility did not change significantly in healthy subjects. Patients with microalbuminuria showed greater reduction in hand joint mobility than diabetic patients with normal UAE or than healthy subjects (p < 0 001). Conclusions. In type 1 diabetic patients, the severity of LJM progresses with time, and the progression is enhanced in patients with microalbuminuria

Care for Women with Delusional Disorder : towards a Specialized Approach

Delusional disorder is a difficult-to-treat clinical condition with health needs that are often undertreated. Although individuals with delusional disorder may be high functioning in daily life, they suffer from serious health complaints that may be sex-specific. The main aim of this narrative review is to address these sex-specific health needs and to find ways of integrating their management into service programs. Age is an important issue. Delusional disorder most often first occurs in middle to late adult life, a time that corresponds to menopause in women, and menopausal age correlates with increased development of both somatic and psychological health problems in women. It is associated with a rise in the prevalence of depression and a worsening of prior psychotic symptoms. Importantly, women with delusional disorder show low compliance rates with both psychiatric treatment and with medical/surgical referrals. Intervention at the patient, provider, and systems levels are needed to address these ongoing problems

Routine cerebrospinal fluid parameters as biomarkers in first-episode psychosis: A prospective observational study

In recent years, multiple studies have investigated the role of biomarkers in first-episode psychosis (FEP) to facilitate early diagnosis, disease stratification, therapeutic choice and outcome prediction. Few studies have focused on cerebrospinal fluid (CSF) investigations. In this prospective observational study, 95 FEP inpatients were followed up for one year. A lumbar puncture was performed at index admission (baseline) to study the CSF parameters (glucose, total proteins, lactate dehydrogenase [LDH], and pleocytosis). At the baseline visit, the clinical assessment included prodromal (psychotic and non-psychotic) symptoms before the psychotic outbreak and psychopathology at admission. The SCID-I was administered to obtain a clinical diagnosis at baseline and at 12 months. The relationship between prodromal and psychopathology symptoms at the baseline visit was tested with multiple linear regression. Multinomial logistic regression was also used to explore the association between CSF biomarkers and longitudinal diagnoses at follow-up (schizophrenia/schizoaffective disorder vs unipolar/bipolar depression vs other psychoses). Higher CSF glucose was associated with depressive (Standardized beta = 0.27, p = 0.041) and disorganized/concrete symptoms (Standardized beta = 0.33, p = 0.023) and lower CSF LDH was associated with prodromal symptoms (Standardized beta = −0.25, p = 0.042). Lower LDH concentrations were also associated with social withdrawal (r = −0.342, p = 0.001). CSF glucose was a predictor of the long-term diagnosis (lower CSF concentrations were associated with schizophrenia or schizoaffective disorder diagnoses [OR = 0.88, CI95%: 0.77–0.99). Our study suggests that CSF biomarkers that involve bioenergetic systems are associated with prodromal symptoms and the phenotype of psychotic disorders during the early stages of the disease

Hormone Targets for the Treatment of Sleep Disorders in Postmenopausal Women with Schizophrenia: A Narrative Review

While the early identification of insomnia in patients with schizophrenia is of clinical relevance, the use of specific compounds to treat insomnia has been studied less in postmenopausal women with schizophrenia. We aimed to explore the effects of melatonin, sex hormones, and raloxifene for the treatment of insomnia in these populations. Although melatonin treatment improved the quality and efficiency of the sleep of patients with schizophrenia, few studies have explored its use in postmenopausal women with schizophrenia. The estrogen and progesterone pathways are dysregulated in major psychiatric disorders, such as in schizophrenia. While, in the context of menopause, a high testosterone-to-estradiol ratio is associated with higher frequencies of depressive symptoms, the effects of estradiol and other sex hormones on sleep disorders in postmenopausal women with schizophrenia has not been sufficiently investigated. Raloxifene, a selective estrogen receptor modulator, has shown positive effects on sleep disorders in postmenopausal women. Future studies should investigate the effectiveness of hormonal compounds on insomnia in postmenopausal women with schizophrenia

Women Undergoing Hormonal Treatments for Infertility: A Systematic Review on Psychopathology and Newly Diagnosed Mood and Psychotic Disorders

Background: The association between infertility treatments and mental disorders has been poorly addressed. This work aims to review current evidence on the psychopathological effects of hormonal treatments used for infertility on women and the occurrence of newly diagnosed mood and psychotic disorders. Methods: A systematic review was performed by searching PubMed and clinicaltrials.gov databases from inception until September 2019. Clinical trials on hormone treatments for infertility in patients with mood or psychotic disorders, as well as those evaluating the onset of symptoms, were included. Selected studies were published in English, Spanish, and Dutch language peer-reviewed journals. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. Observational studies and case reports were excluded. Effect sizes for changes in depressive symptoms were calculated with Hedges'g and Cohen's d confidence intervals. A meta-analysis was not performed due to the heterogeneity of hormonal compounds in protocols. Results: From 1,281 retrieved records, nine trials were included; all of them were conducted in non-clinical populations. Four trials compared Gonadotropin-releasing hormone (GnRH) agonists and GnRH antagonists, showing a better mood profile for hormonal protocols including antagonists in one trial. Two trials compared protocols using GnRH agonists/antagonists versus natural cycle protocols (without gonadotropin stimulation), with a better mood profile (less depressive symptoms) in those protocols without gonadotropin stimulation. Other studies compared long and short protocols of GnRH agonists (no differences); two GnRH agonists, buserelin, and goserelin (no differences); and two patterns of clomiphene vs placebo administration (no differences). None of the selected studies investigated the risk of relapse in women with a previous diagnosis of depressive or psychotic disorders. When exploring pre-post changes in depressive symptoms, effect sizes suggested mild mood worsenings for most protocols (effect sizes ≤ -0.4), with the following pattern (worse to better): GnRH agonist > GnRH antagonist > no gonadotropin stimulation. Conclusions: This is the first systematic review exploring the psychopathological effects of hormonal infertility treatments. Our study suggests that protocols without gonadotropin stimulation show a better mood profile when compared to those using GnRH antagonists or GnRH agonists. Future studies need to include patients with major mood and psychotic disorders

BDNF genetic variants and methylation: effects on cognition in major depressive disorder

Brain-derived neurotrophic factor (BDNF) gene regulation has been linked to the pathophysiology of major depressive disorder (MDD). MDD patients show cognitive deficits, and altered BDNF regulation has a relevant role in neurocognitive functions. Our goal was to explore the association between BDNF genetic and epigenetic variations with neurocognitive performance in a group of MDD patients and healthy controls considering possible modulating factors. The sample included 134 subjects, 64 MDD patients, and 70 healthy controls. Clinical data, childhood maltreatment, and neurocognitive performance were assessed in all participants. Eleven single nucleotide polymorphisms (SNPs) and two promoter regions in the BDNF gene were selected for genotype and methylation analysis. The role of interactions between BDNF genetic and epigenetic variations with MDD diagnosis, sex, and Childhood Trauma Questionnaire (CTQ) scores was also explored. We observed significant associations between neurocognitive performance and two BDNF SNPs (rs908867 and rs925946), an effect that was significantly mediated by methylation values at specific promoter I sites. We identified significant associations between neurocognitive results and methylation status as well as its interactions with MDD diagnosis, sex, and CTQ scores. Our results support the hypothesis that BDNF gene SNPs and methylation status, as well as their interactions with modulating factors, can influence cognition. Further studies are required to confirm the effect of BDNF variations and cognitive function in larger samples.This study was supported in part by grants from the Carlos III Health Institute through the Ministry of Economy and Competitiveness (PI10/01753, PIE14/00034 and PI15/00662), co-funded by the European Regional Development Fund (ERDF) “A way to build Europe”, CIBERSAM, and the Catalan Agency for the Management of University and Research Grants (AGAUR 2017 SGR 1247). We also thank CERCA Programme/ Generalitat de Catalunya for institutional support. The genotyping and methylation services were carried out at CEGEN-PRB3-ISCIII and were supported by grants PT13/0001 and PT17/0019, ISCIII-SGEFI/FEDER. Dr. Labad received an Intensification of the Research Activity Grant (SLT006/17/00012). Dr. Costas was supported by a Miguel Servet II contract from the Carlos III Health Institute (CPII16/00019). Dr. Soriano-Mas was supported by a Miguel Servet contract from the Carlos III Health Institute (CPII16/00048)S

Risk factors for metabolic syndrome in individuals with recent-onset psychosis at disease onset and after 1-year follow-up

Metabolic syndrome (MetS) is a cluster of parameters encompassing the most dangerous heart attack risk factors, associated with increased morbidity and mortality. It is highly prevalent in recent-onset psychosis (ROP) patients. In this pilot study, we evaluated MetS parameters (fasting glucose, high-density lipoprotein (HDL) cholesterol (HDL-c), fasting triglycerides, waist circumference, and systolic and diastolic blood pressure), clinical symptoms, pharmacological treatment, lifestyle, and inflammatory markers in 69 patients with ROP and 61 healthy controls (HCs). At baseline, waist circumference (p = 0.005) and fasting triglycerides (p = 0.007) were higher in patients with ROP than in HCs. At the 1-year follow-up, patients showed clinical improvement, with a reduction in the positive and negative syndrome scale (PANSS) score (p < 0.001), dietary intake (p = 0.001), and antipsychotic medication dose (p < 0.001); however, fasting glucose (p = 0.011), HDL-c (p = 0.013) and waist circumference worsened (p < 0.001). We identified sex, age, BMI, dietary intake, physical activity, daily tobacco use, daily cannabis use, and antipsychotic doses as risk factors contributing to baseline MetS parameters. After 1-year follow-up, those factors plus the PANSS and Calgary Depression Scale for Schizophrenia (CDSS) scores were associated with MetS parameters. Further studies are needed to understand the contributions of the studied risk factors in patients with ROP at onset and during disease progression