Biomarkers of Bipolar Disorder in Late Life: An Evidence-Based Systematic Review.

PURPOSE OF REVIEW: Review the current evidence on biomarkers for bipolar disorder in the older adults. We conducted a systematic search of PubMed MEDLINE, PsycINFO, and Web of Science databases using the MeSH search terms "Biomarkers", "Bipolar Disorder", "Aged" and and "Aged, 80 and over". Studies were included if they met the following criteria: (1) the mean age of the study population was 50 years old or older, (2) the study included patients with bipolar disorder, and (3) the study examined one type of biomarkers or more including genetic, neuroimaging, and biochemical biomarkers. Reviews, case reports, studies not in English and studies for which no full text was available were excluded. A total of 26 papers were included in the final analysis. RECENT FINDINGS: Genomic markers of bipolar disorder in older adults highlighted the implication of serotonin metabolism, while the expression of genes involved in angiogenesis was dysregulated. Peripheral blood markers were mainly related with low grade inflammation, axonal damage, endothelial dysfunction, and the dysregulation of the HPA axis. Neuroanatomical markers reflected a dysfunction of the frontal cortex, a loss of neurones in the anterior cingulate cortex and a reduction of the hippocampal volume (in patients older than 50 years old). While not necessarily limited to older adults, some of them may be useful for differential diagnosis (neurofilaments), disease staging (homocysteine, BDNF) and the monitoring of treatment outcomes (matrix metalloproteinases). Our review provides a comprehensive overview of the current evidence on biomarkers for bipolar disorder in the older adults. The identification of biomarkers may aid in the diagnosis, treatment selection, and monitoring of bipolar disorder in older adults, ultimately leading to improved outcomes for this population. Further research is needed to validate and further explore the potential clinical utility of biomarkers in this population.

A comprehensive study of medically serious suicide attempts in France: incidence and associated factors.

AIMS: People who make medically serious suicide attempts (MSSAs) share a number of features with those who die by suicide, and are at a high risk of suicide themselves. Studies to date have mostly focused on clinical samples of MSSAs. An epidemiological examination at a national level can help to identify risk profiles and pathways of care in this population. METHODS: We explored the French nationwide hospital discharge database (Programme de Médicalisation des Systèmes d'Information, PMSI) to identify any MSSA taking place between 2012 and 2019. Relevant demographic and medical information was collected about the first MSSA of each attempter. Data from 2010 and 2011 were used to verify the absence of prior attempts. RESULTS: First occurrences of MSSAs amounted to 81 959 cases over 8 years, with a mean age of 45.8 years, and 53.6% women. Incidence was higher in women (18.1 v. 17.3 per 1 00 000). The most common suicide method was deliberate self-poisoning (64.9% of cases). In comparison, violent methods associated higher mortality and comorbidity and were more frequent in men. The most common mental disorders were mood disorders (55.6%) and substance use disorders (46.2%). A minority of MSSA survivors were hospitalised in psychiatry (32.5%), mostly women. CONCLUSIONS: MSSAs are frequent and easy to identify. There is a need to reinforce the continuity of psychiatric care for this population given the high risk of subsequent suicide, and the low rates of psychiatric hospitalisation after an MSSA even if violent methods are used. Specific care targeting this population could reduce treatment gaps.

Exploring the boundaries between borderline personality disorder and suicidal behavior disorder.

OBJECTIVE: To compare clinical traits of suicidal vulnerability among in-patients with suicidal behavior disorder (SBD) with and without borderline personality disorder (BPD). METHOD: we recruited adult patients with SBD, consecutively and voluntarily hospitalized in a specialized unit for affective disorders and suicidal behavior between July and October 2016. Ninety-two inpatients having attempted suicide within the past 2 years were divided into two subgroups according to the presence or absence of BPD. Clinical vulnerability traits for suicidal behavior were assessed. RESULTS: Half of the patients with SBD also had BPD. Patients with BPD were nine times more likely to be major suicide repeaters compared to those without. They were also more likely to display clinical and psychological vulnerability traits for suicidal behavior, even after considering potential confounders. Emotional dysregulation, shame-proneness, impulsiveness, preoccupied attachment pattern, and childhood trauma were high in both groups, but significantly increased in those with (vs. without) BPD status. Psychological traits remained stable in SBD-BPD patients, regardless of the time since the last suicide attempt (i.e. SBD in recent vs. early remission). CONCLUSIONS: Clinical and psychological traits associated with suicidal vulnerability are present in all SBD patients compared to non-suicidal populations, but comorbidity with BPD is associated with particularly high scores. BPD could be considered as a specifier for SBD diagnoses.

Association of symptoms of attention deficit-hyperactivity disorder and impulsive-aggression with severity of suicidal behavior in adult attempters.

Literature emphasizes the relationship between attention deficit-hyperactivity disorder (ADHD) and suicidal behavior (SB). However, the link between ADHD and the severity of SB is yet to be determined. We investigated the association between a probable diagnosis of ADHD and the severity of SB in 539 hospitalized suicide attempters, and determined the role of comorbid psychiatric diagnoses. The severity of SB was defined as the number of suicide attempts, age at first suicide attempt, seriousness and violence of suicide attempts. A diagnosis of probable adult ADHD (probable ADHD) was defined as the presence of both current ADHD symptoms and ADHD symptoms in childhood. We evaluated the combined effect of high impulsive-aggression levels and probable ADHD. Probable ADHD was not associated with early or frequent suicide attempts after adjustment for psychiatric disorders and treatment intake. High levels of impulsive-aggression increased the risk of an early suicide attempt, particularly in patients with ADHD symptoms, and independently of other clinical factors. The association between serious suicide attempts and probable ADHD remained significant after adjustment. Although ADHD is involved in suicidal vulnerability, psychiatric comorbidities and impulsive-aggression appear to largely explain the severity of SB in adult attempters with ADHD symptoms.

Tianeptine is associated with lower risk of suicidal ideation worsening during the first weeks of treatment onset compared with other antidepressants: A naturalistic study.

Worsening of suicidal ideation during the first weeks of antidepressant treatment is a poorly understood phenomenon that prompted regulatory bodies to issue specific warnings. To better understand the causes of this phenomenon, this study compared the risk of suicidal ideation worsening in patients taking different types of antidepressant medications. To this aim, 4017 depressed adult outpatients were followed by general practitioners and psychiatrists throughout France for 6 weeks after prescription of an antidepressant treatment. The main study outcomes were to monitor changes (worsening or improvement) in suicidal ideation between baseline (treatment onset) and the study end (week 6) and to determine the remission rates according to the treatment type. Depression severity was assessed with the patient-administered Hospital Anxiety and Depression Scale and suicidal ideation with the 9-item Montgomery-Asberg Depression Rating Scale and the Hopelessness Scale. Use of tianeptine, a mu-opioid receptor agonist was significantly associated with a lower risk of suicidal ideation worsening compared with other antidepressants in the first 6 weeks of treatment. Conversely, remission rates were not significantly affected by the treatment type. Our results highlight a potential interest of opioid agonists to reduce the risk of worsening of suicidal ideation at antidepressant initiation.

How far is clinical assessment from the bullseye? Using MEmind to compare clinical assessment with self-assessment in patients with depression and anxiety diagnosis

Background and objectives: Technology based assessments are being used for screening and monitoring in a wide scope of medical specialties, including mental health field. Depression and anxiety are common disorders in which e-health tools can be useful. We aimed to compare clinician assessment of illness severity in patients with depression and anxiety diagnosis with computer-based self-assessment within 24h of clinician evaluation via MEmind (www.memind.net), a novel web-tool. Methods: From May 2014, adult patients attended in outpatient settings in Fundación Jiménez Diaz Psychiatry Department were registered in MEmind, a web tool designed for psychiatric assessment. During the recruitment, clinicians use CGI-S for patient assessment via MEmind and provide patients a code and password to use the web-tool. We selected those patients diagnosed with depression and/or anxiety who connected within 24h of the clinical visit and complete in the web page GHQ and WHO-5 scales. We calculated a bivariate correlation for CGI-S, WHO-5 and GHQ-12. Results: Of the 231 participants, 157 (68%) were diagnosed with anxiety disorders and 74 (32%) with depression. Using the Spearman Rho test for correlation, we found a low correlation between CGI-S and total WHO-5 (r=−0.192; p=0.006) and between CGI-S and total GHQ-12 (r=0.211; p=0.002) and a good correlation between total WHO-5 and total GQH-12 (r=−0.606; p=0.000). Conclusions: We found a low correlation between clinician assessment and patients’ self-reports within 24h of clinician evaluation. Factors that potentially influenced the degree of correlation related with patients, clinicians, measurements and technology are discussed

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Effect of early trauma on the sleep quality of euthymic bipolar patients.

OBJECTIVE: Poor quality of sleep is frequent in euthymic bipolar patients and conveys worse clinical outcomes. We investigated the features of euthymic bipolar patients associated with poor sleep quality, with a focus on the effect of childhood trauma. METHOD: 493 euthymic patients with DSM-IV-defined bipolar disorders were recruited in FondaMental Advanced Centers of Expertize for Bipolar Disorders (FACE-BD) between 2009 and 2014. Clinical variables were recorded. Subjective sleep quality and history of childhood trauma were respectively measured by the Pittsburgh Sleep Quality Index (PSQI) and the Childhood Trauma Questionnaire (CTQ). RESULTS: Poor sleepers were older, less professionally active, had significantly higher anxiety levels, took more anxiolytic drugs and did endorse more suicide attempts and suicidal ideas than good sleepers after adjusting for anxiety levels and age. Emotional abuse was associated with poor sleep quality after adjustment for BMI, age, professional activity, and bipolar disorders (BD) type (OR=1.83; 95% CI [1.30; 3.10]; p=0.02). However, this association was lost after adjustment for anxiety levels, anxiolytic treatment and suicide ideation/attempts. LIMITATIONS: The main limitation was the type of sleep assessment, which only measured the subjective part of sleep complaints. CONCLUSION: A history of emotional abuse might underlie sleep problems in many bipolar patients but anxiety seems to act as a confounding factor in this relationship. New studies are needed to elucidate the role of childhood maltreatment on poor sleep among bipolar patients.

Computerized Adaptive Test vs. decision trees: Development of a support decision system to identify suicidal behavior.

BACKGROUND: Several Computerized Adaptive Tests (CATs) have been proposed to facilitate assessments in mental health. These tests are built in a standard way, disregarding useful and usually available information not included in the assessment scales that could increase the precision and utility of CATs, such as the history of suicide attempts. METHODS: Using the items of a previously developed scale for suicidal risk, we compared the performance of a standard CAT and a decision tree in a support decision system to identify suicidal behavior. We included the history of past suicide attempts as a class for the separation of patients in the decision tree. RESULTS: The decision tree needed an average of four items to achieve a similar accuracy than a standard CAT with nine items. The accuracy of the decision tree, obtained after 25 cross-validations, was 81.4%. A shortened test adapted for the separation of suicidal and non-suicidal patients was developed. CONCLUSION: CATs can be very useful tools for the assessment of suicidal risk. However, standard CATs do not use all the information that is available. A decision tree can improve the precision of the assessment since they are constructed using a priori information.

Predictors of psychological distress in advanced cancer patients under palliative treatments.

This work aims to investigate the factors associated with psychological distress in advanced cancer patients under palliative treatment. We comprehensively assessed the demographic, psychosocial and health factors of 158 advanced cancer patients. Patients with high and low distress, according to the Hospital Anxiety and Depression Scale, were compared. A regression analysis was built to identify the best predictors of distress. Patients with high psychological distress (81%) were more likely to have lung cancer, suicidal ideation, hopelessness, low quality of life and poor body image than those without. In the multivariate model, only poor emotional functioning (OR = .89; 95% CI = .83-.95; p ≤ .001), hopelessness (OR = .86; 95% CI = .78-.94; p ≤ .001) and body image distortions (OR = .77; 95% CI = .68-.85; p = .005) were retained. High levels of hopelessness, impaired emotional functioning and body image distortions are the main factors associated with psychological distress in patients with advanced cancer. Potential interventions to modify these factors in palliative units are discussed.

Suicide mortality trends in Galicia, Spain and their relationship with economic indicators.

BACKGROUND: Recent research has shown an association between unemployment and suicide, but the mediating factors in this relationship are still unknown. In this study, we investigated the effect of unemployment and economic recession on suicide rates in the Spanish region of Galicia between 1975 and 2012 Method. We analysed age-standardised suicide rates in men and women and in four age groups: less than 25 years, 25-45 years, 45-65 years and more than 65 years and performed a joinpoint analysis to determine trend changes throughout 1975-2012 period. Also we analysed the association between suicide, recession and unemployment by means of a temporal trend model with a Generalised Additive Model. RESULTS: Suicide rates increased from 145 suicides in 1975 to a high in 1993, with 377 deaths by suicide, representing 1.38% of all causes of death, and thereafter they tend to decrease to 335 suicides in 2012. Joinpoint analyses revealed that suicide rates changed differently across sex and age groups. For men, the annual percentage of change (APC) between 1975 and 1988 (CI 95% 1986-1994) was 5.45 (CI 95% = 3.5, -7.2) but from 1988 the APC became negative [-0.66 (CI 95% = -1.3, -0.1)]. For women, APC between 1974 and 1990 (CI 95% 1986-1992) was 4.86 (CI 95% = 3.2, -6.4) and -1.46 subsequently (CI 95% = -2.2, -0.5). Women aged 24 years or less showed stable suicide rates while men from 45-65 years showed two incidence peaks. When we studied the independent correlation between unemployment, recession and suicide, we found a significant association between unemployment and suicide, but not between recession and suicide for both sexes together and for men while for women there was no significant correlation between suicide and unemployment or recession. Finally, when we studied the effect of the interaction between unemployment and recession on suicide we found economic recession and unemployment interacted with regards to suicide rates (F = 5.902; df = 4.167; p = 0.00098) and after adjusting by sex, the effect was confirmed among men (F = 4.827; df = 2.823; p = 0.0087), but not among women (F = 0.001; df = 1.000; p = 0.979). CONCLUSIONS: Although suicide rates in Galicia are gradually decreasing in the last decades, there are important sex and age differences. Unemployment was related with suicide during economic recession periods according to our results.

Suicide ideation among oncologic patients in a Spanish ward.

Oncologic patients are exposed to a higher risk of suicidal behaviors than the general population. In this study, we aim to examine the severity of suicidal ideation in a sample of oncologic patients considering different psychological and clinical features. We interviewed 202 inpatients receiving curative or palliative treatment in a medical oncology ward of a Spanish hospital during the period 2012-2014. A complete assessment of psychosocial factors, cancer diagnoses (lung, colon rectum, and genitourinary system), and suicidal behaviors were made during admission, including validated questionnaires about depression, anxiety, personality, quality of life, body image, life threatening events, hopelessness, and suicidal ideation. The characteristics of inpatients with high and low suicidal ideation were retrospectively compared. A logistic regression model was constructed to examine the relationship between the significant factors retained after the univariate analyses. One of every four patients (n = 51; 25.24%) presented high scores of suicidal ideation. Logistic regression analyses retained depression (OR = 3.55; 95% CI = 1.25-11.68; p = .016), hopelessness (OR = 8.78; 95% CI = 3.44-25.88; p ≤ .001), personality (OR = .44; 95% CI = .2-.96; p = .038), and advanced age (OR = 2.60; 95% CI = 1.18-5.98; p = .016) as the main risk factors for high suicidal ideation. Suicidal ideation was frequent among oncologic patients. These patients should receive closer monitoring, especially, when old, retired, or severely depressed.

The additive effect on suicidality of family history of suicidal behavior and early traumatic experiences.

Family history of suicidal behavior and personal history of childhood abuse are reported risk factors for suicide attempts and suicide completion. We aim to quantify the additive effect of family history of suicidal behavior and different subtypes of childhood abuse on suicidal behavior. We examined a sample of 496 suicide attempters, comparing individuals with family history of suicidal behavior and personal history of childhood (physical or sexual) abuse, individuals with family history of suicidal behavior only, individuals with history of early traumatic experiences only, and individuals with none of these two risk factors with regards to suicidal features. An additive effect was found for the age at the first attempt in suicide attempters with both family history of suicidal behavior and either physical or sexual abuse. No significant interactions were found between family history of suicidal behavior and childhood trauma in relation to any characteristics of suicidal behavior. Subjects presenting family history of suicidal behavior and childhood abuse attempt suicide earlier in life than subjects with just one or none of them, particularly if they were sexually abused. Other suicidality indexes were only partially or not associated with this combination of risk factors. A careful assessment of patients with both family history of suicidal behavior and childhood abuse could help to prevent future suicide attempts, particularly in young people.

Increased severity of suicidal behavior in impulsive aggressive patients exposed to familial adversities.

BACKGROUND: The mechanisms by which childhood abuse and family history of suicidal behavior (FHS) lead to an increased risk of suicidal behavior are still unknown. Impulsive aggression may play an intermediate role. We investigated whether greater scores for aggression and impulsivity might be associated with the effects of FHS and/or childhood abuse on the severity of suicidal behavior. METHOD: We examined the scores of three scales measuring impulsive aggression in a sample of 696 suicide attempters. We compared the highest and lowest scores with regard to reports of childhood abuse and FHS using adjusted multinomial regression models. Genetic polymorphisms of the serotonergic system known to be associated with impulsive aggression were also analyzed. RESULTS: Patients with high impulsive aggressive scores showed significant differences in sociodemographic, clinical and suicidal features compared with patients with low impulsive aggressive scores. Adjusted results showed that combinations of some types of childhood abuse and FHS, particularly emotional abuse and emotional neglect, are associated with high impulsivity and hostility scores. The SS genotype of the serotonin transporter gene (5-HTTLPR) was associated with high levels of impulsivity when the subjects reported emotional abuse [odds ratio (OR) 5.55, 95% confidence interval (CI) 1.75-17.5] or physical abuse (OR 5.03, 95% CI 1.50-16.9) in their childhood. CONCLUSIONS: Our results support the role of impulsive aggression as one of the links that may connect childhood abuse and FHS with severity of suicidal behavior.

Association of common genetic variants with risperidone adverse events in a Spanish schizophrenic population.

Risperidone non-compliance is often high due to undesirable side effects, whose development is in part genetically determined. Studies with genetic variants involved in the pharmacokinetics and pharmacodynamics of risperidone have yielded inconsistent results. Thus, the aim of this study was to investigate the putative association of genetic markers with the occurrence of four frequently observed adverse events secondary to risperidone treatment: sleepiness, weight gain, extrapyramidal symptoms and sexual adverse events. A series of 111 schizophrenia inpatients were genotyped for genetic variants previously associated with or potentially involved in risperidone response. Presence of adverse events was the main variable and potential confounding factors were considered. Allele 16Gly of ADRB2 was significantly associated with a higher risk of sexual adverse events. There were other non-significant trends for DRD3 9Gly and SLC6A4 S alleles. Our results, although preliminary, provide new candidate variants of potential use in risperidone safety prediction.

Suicidal phenotypes associated with family history of suicidal behavior and early traumatic experiences.

BACKGROUND: Family history of suicidal behavior and personal history of childhood trauma are risk factors for suicidal behaviors. We hypothesize that subjects with any of these risk factors will show differential features and that subjects with both of them will display more severe phenotypes. METHODS: This study compares three groups of suicide attempters (n=878): subjects with a family history of suicidal behavior and a personal history of early traumatic experiences, subjects with a family history of suicidal behavior or a personal history of early traumatic experiences, and subjects with neither of these two risk factors, with regards to psychopathology, personality traits and suicidal behavior. RESULTS: Subjects with a family history of suicidal behavior and childhood trauma were younger at their first suicide attempt and made more frequent, severe and violent attempts when compared with the other groups. Differences in number and precocity of attempts remained after adjustments in a multinomial regression model. Finally, personality profiles were also substantially different in the group with higher impulsiveness, novelty seeking, affective lability and hopelessness. LIMITATIONS: The information provided by subjects regarding childhood abuse and family history of suicidal behavior was not confirmed by other sources. CONCLUSIONS: Suicide attempters with a family history of suicidal behavior and childhood trauma show specific characteristics that might be used to prevent future suicidal behaviors in this population. Both risk factors should be routinely investigated when assessing the suicidal risk of a patient.

Cost-efficiency of laboratory testing among psychiatric inpatients.

BACKGROUND: A set of tests to rule out medical conditions among psychiatric inpatients is still to be defined. A first step in this direction is to determine the utility of lab tests commonly used by psychiatrists. METHODS: Biochemical tests have been routinely performed on inpatients in a psychiatric hospitalization unit from 2006 to 2009. This study examines the prevalence of abnormal values in 1,278 laboratory tests performed on 894 patients. The number of subjects screened and the direct expenditure needed to find results outside the normal range were computed. Differences in clinical profiles were compared between diagnostic groups according to main diagnosis. RESULTS: We found high rates of seropositive patients for human immunodeficiency virus (14.3%) and hepatitis B virus (15.7%). Most patients met at least one criteria of metabolic syndrome (67.6%). The detection of hepatic abnormalities was very efficient (65.71%), particularly for patients diagnosed with alcohol use disorders. CONCLUSIONS: The cost-efficiency of lab tests in psychiatric units is greatly variable. Though results of this study may not be generalized due to the different prevalence of medical conditions, the methodology can be easily implemented across psychiatric services. Cost-effectiveness and costbenefit analyses are warranted.

[Electronic calendar as an organization element in Internal Medicine services]. / Los calendarios electrónicos como herramientas de organización de los servicios de Medicina Interna.

The growing volume of information and introduction of new technologies in the Internal Medicine hospital department mare making the traditional updating «methods¼ of knowledge and organization obsolete. The development of new tools could help the management of information and organization of the medical departments is outdated. Electronic calendar such as the Google calendar facilitate adequate coordination among health care professionals. Our experience suggests that the Google calendar is a simple and useful tool that helps planning and organization of the clinical, educational, and research activities of the different medical departments, limits loss of information and improves efficacy with a close to zero cost of infrastructure.

Los calendarios electrónicos como herramientas de organización de los servicios de Medicina Interna / Electronic calendars as an organization element in Internal Medicine services

El volumen creciente de información y la introducción de las nuevas tecnologías en los servicios hospitalarios de Medicina Interna hacen que los «métodos» tradicionales de actualización de conocimientos y organización se hayan quedado obsoletos. El desarrollo de nuevas herramientas podría ayudar en la gestión de la información y organización de los servicios médicos. Los calendarios electrónicos como el Google calendar facilitan la coordinación de los profesionales de la salud. Nuestra experiencia sugiere que Google calendar es una herramienta que facilita la organización de la actividad asistencial, docente y de investigación de los servicios médicos, limita la pérdida de información, y mejora su eficiencia con un coste de infraestructura prácticamente nulo(AU)

The growing volume of information and introduction of new technologies in the Internal Medicine hospital department mare making the traditional updating «methods» of knowledge and organization obsolete. The development of new tools could help the management of information and organization of the medical departments is outdated. Electronic calendars such as the Google calendar facilitate adequate coordination among health care professionals. Our experience suggests that the Google calendar·is a simple and useful tool that helps planning and organization of the clinical, educational, and research activities of the different medical departments, limits loss of information and improves efficacy with a close to zero cost of infrastructure(AU)

Retraso mental como factor de riesgo para el desarrollo de un trastorno psicótico / Mental retardation as a risk factor to develop a psychotic disease

Introducción. En las últimas tres décadas uno de los principales objetivos de la investigación en esquizofrenia ha sido la identificación de los síntomas y signos precursores de la enfermedad antes de su aparición. Objetivo. Buscamos en nuestro estudio los antecedentes que se otorgan previamente a pacientes antes de ser filiados como esquizofrenia. Método. Se trata de un estudio caso-control sobre el que utilizamos un registro de datos que incluye los campos del Conjunto Mínimo Básico de Datos y el período de tiempo considerado fue entre 1999-2005. Resultados. Encontramos una frecuencia de 3,6% de retraso mental y un 2,1% de antecedentes de trastornos del comportamiento y de las emociones de comienzo habitual en la infancia y adolescencia, ambos como diagnóstico previo. La odds ratio de que un paciente con retraso mental sufra psicosis en la edad adulta es de 4,6 (IC 95% [3,43-6,26]), esquizofrenia de 5,8 [IC 95% (4,20-7,88)], esquizofrenia paranoide de 4,8 (IC 95% [3,39 –6,93]), esquizofrenia residual de 7,0 (IC 95% [4,81 -10,09]), trastorno por ideas delirantes de 2,7 (IC 95% [1,57 -4,73]). Conclusiones. De nuestro estudio se puede concluir que existe una frecuencia incrementada del diagnóstico de retraso mental entre los antecedentes patológicos de sujetos que posteriormente serán diagnosticados de esquizofrenia paranoide y esquizofrenia residual. Este hecho, supone un apoyo a la hipótesis etiológica de la esquizofrenia que involucra alteraciones en el neurodesarrollo (AU)

Introduction. One of the main aims of research on schizophrenia has been to pinpoint the early symptoms and signals of the disease before its appearance. Objectives. We have examined the diagnoses previously given to patients before they were diagnosed of schizophrenia. Method. This is a case-control study in which we used a data register including the fields of minimum basic data set (MBDS) whose time period included 1999 to 2005. Results. In our study, there was a 3.6% frequency of mental retardation and 2.1% one of behavioral and emotional disorders with onset usually occurring in childhood and adolescence, both diagnosed previously. The estimated odds ratio for a mentally retarded patient to suffer adult onset psychosis is 4.6 (95%CI [3.43-6.26]), schizophrenia 5.8 (95% CI [4.20-7.88]), paranoid schizophrenia 4.8 (95% CI [3.39 –6.93]), residual schizophrenia 7.0 (95% CI [4.81 -10.09]) and persistent delusional disorder 2.7 (95% CI [1.57 -4.73]). Conclusions. It can be concluded from our study that there is an increased frequency of mental retardation among the pathological records of subjects who will be diagnosed with paranoid schizophrenia and residual schizophrenia in the future. This fact supports the etiological thesis of schizophrenia (AU)