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The gene coding for catecol-o-methyltransferase (COMT), participant in the metabolism of catecholamines, has long been implicated as a candidate gene for schizophrenia. We determined the relation of the COMT Val108/158Met polymorphism with schizophrenia or its symptomatology (negative, disorganized and psychotic dimension). We conducted a case–control study comprising 186 patients with schizophrenia and 247 controls. The diagnosis of schizophrenia was established using the DSM-IV criteria for this illness. The clinical symptomatology was assessed through the Scale for the Assessment of Negative Symptoms and the Scale for the Assessment of Positive Symptoms. No significant differences were found in the distribution of alleles (χ2 = 0.01, df = 1, p = 0.90) or genotypes (χ2 = 1.66, df = 2, p = 0.43) between schizophrenic patients and the control group. Multivariate analysis showed that the COMT Val108/158Met polymorphism has no influence in the clinical symptomatology of schizophrenia. Our results showed no association between COMT Val108/158Met and schizophrenia or evidence for an association between COMT and the clinical symptomatology of this illness. This suggests that the COMT gene may not contribute to the risk for schizophrenia among the Mexican population.

This paper describes the procedure to obtain some DNA probes likely to be good candidate genes for mapping major psychiatric disorders. The advantages in using this mapping strategy are discussed as well.

Subtypes of obsessive-compulsive disorder (OCD) related to age could determine differential response to treatment. To explore possible age differences in the effect of clomipramine in an animal model of OCD. The deficits on spontaneous alternation produced by 8-OH-DPAT and the preventing actions of clomipramine, desipramine and WAY 100635 were compared between young and adult rats. No age differences were found in spontaneous alternation. The 5-HT1A agonist, 8-OH-DPAT (0.031, 0.125, 0.5 and 2.0 mg/kg, −15 min) produced perseveration in young and adult rats. However, young rats were sensitive to a lower dose of 8-OH-DPAT. Clomipramine (10 mg/kg per three administrations) completely prevented the action of 8-OH-DPAT (0.5 mg/kg) in adult rats. However, this treatment as well as higher doses (15 mg/kg 3 administrations) or injected for longer periods (10 mg/kg 5 administrations) produced weak protective effects (versus 0.125 mg/kg 8-OH-DPAT) or had no action (versus 0.5 mg/kg 8-OH-DPAT) in young animals. WAY 100 635 (0.5 mg/kg) blocked the action of 8-OH-DPAT (0.5 mg/kg) in both young and adult rats. Desipramine (10 mg/kg/3 administrations) lacked of a preventive effect on the 8-OH-DPAT (0.5 mg/kg) action. This result indicated that the 5-HT1A receptor is involved in the deficits on spontaneous alternation produced by 8-OH-DPAT. The present data shows important age differences in the effect of clomipramine in a model of OCD. Such differences could be relevant for the age variations in the response to treatment in clinical practice.

Obsessive-compulsive disorder (OCD) could be considered a neurodevelopmental disorder, from several lines of evidence. One of the most widely studied genes in these disorders is the apolipoprotein E gene, particularly allele 4. We analyzed for association among patients with OCD versus normal controls and cognitively impaired patients. There were no significant differences between OCD probands compared with population controls. However, the cognitively impaired group showed a higher frequency of allele apolipoprotein E gene compared with normal controls and patients with OCD.

Background Neonatal lesion in the ventral hippocampus (NLVH) is a validated animal model to study schizophrenia from a neurodevelopmental perspective. This animal model is also used to investigate how neonatal lesions may alter the genetic expression of dopaminergic receptors. The present study compares mRNA expression levels of dopamine receptors (drd2 and drd3) in lymphocytes and brain of NLVH animals at two different age stages: young and adult. Methods The NLVH procedure was performed on 20 male Wistar rats at postnatal days 5–7. The mRNA expression levels of drd2 and drd3 genes in lymphocytes, nucleus accumbens, hippocampus and prefrontal cortex were measured and analyzed at postnatal days 45 and 90. The results were compared and contrasted with respective sham groups. Results In lymphocytes, only in NLVH-adult group we observed drd2 mRNA expression, while drd2 mRNA expression was not observed in the NLVH-juvenile rats; on the other hand, the drd3 mRNA expression did not show significant statistical differences. In hippocampus no differences were observed between drd2 mRNA or drd3 mRNA expression when comparing juvenile/adult shams with NLVH groups. In the prefrontal area, a decrease in drd2 mRNA expression levels were observed in the NLVH-adult group (F(1,3) = 52.83, p = 0,005) in comparison to the sham-adult group. Finally, in the nucleus accumbens, a strong decrease of drd3 mRNA expression was observed in the NLVH-adult group in comparison to the sham-adult group (F(1,3) = 123,2, p

A fundamental precondition for early intervention in schizophrenia is accurate detection of prodromal states, that is, sign and symptom constellations that predict the onset of psychosis in persons with no prior background. Several structured interviews have been designed for the detection of prodromal subjects.To translate and determine the reliability of the PRIME Screen in an adolescent community sample in México City.A total of 532 adolescents of a technical-industrial educational center of México City were included for the study. All the subjects were administered the PRIME Screen Questionnaire of Prodromal Symptoms.A total of 98 subjects (18.4%) reported one or more prodromal symptoms. The results of the factorial analysis showed that the PRIME Screen questionnaire is conformed by three factors that explained 59.3% of the variance. Internal consistency of the instrument was of 0.88.Our results on the exploratory factor analysis show that the items of the questionnaire are grouped into three main areas called: a) alteration of setting; b) sensorial-perceptual abnormalities, and c) alterations of self-skills. The Prodromal Symptoms Screen Questionnaire is an instrument with adequate clinimetric behavior that may be effective to conduct community-wide screening of adolescents for prodromal symptoms.

artículo (arbitrado). Universidad de Costa Rica, Centro de Investigación Celular y Molecular, 2006 Two hundred seventeen male subjects from Costa Rica, Mexico, and the Hispanic population of the southwestern United States were studied. Twelve Y-chromosome STRs and the HVSI sequence of the mtDNA were analyzed to describe their genetic structure and to compare maternal and paternal lineages. All subjects are part of two NIMH-funded studies to localize schizophrenia susceptibility genes in Hispanic populations of Mexican and Central American ancestry. We showed that these three populations are similar in their internal genetic characteristics, as revealed by analyses of mtDNA and Y-chromosome STR diversity. These populations are related through their maternal lineage in a stronger way than through their paternal lineage, because a higher number of shared haplotypes and polymorphisms are seen in the mtDNA (compared to Y-chromosome STRs). These results provide evidence of previous contact between the three populations and shared histories. An analysis of molecular variance revealed no genetic differentiation for the mtDNA for the three populations, but differentiation was detected in the Y-chromosome STRs. Genetic distance analysis showed that the three populations are closely related, probably as a result of migration between close neighbors, as indicated by shared haplotypes and their demographic histories. This relationship could be an important common feature for genetic studies in Latin American and Hispanic populations. Universidad de Costa Rica UCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias Básicas::Centro de Investigación en Biología Celular y Molecular (CIBCM)

Systematic investigations indicate that some of the recognized psychiatric disorders can be identified among those with mental retardation due to chromosomal abnormalities. We report a psychotic patient with mild mental retardation (intelligence quotient: 68) and minor anomalies that had a chromosomal aberration not previously described in a psychotic patient. Our patient highlights the importance of the cytogenetic study in psychiatric patients with comorbid mental retardation or minor anomalies. In addition, her psychosis symptoms may be helpful to propose a new candidate gene for psychosis.

The molecular analysis of the human phenylalanine hydroxylase (PAH) gene in Mexican phenylketonuric (PKU) patients is described. We analyzed the restriction fragment length polymorphism (RFLP) haplotypes of five probands and ten non-affected relatives, belonging to four unrelated PKU families. Twenty-nine alleles were typified, corresponding to 12 different haplotypes. Eight RFLP haplotypes corresponded to those described in other populations, while the remaining were unreported haplotypes, appearing both on normal and PKU chromosomes. Using the polymerase chain reaction (PCR) and the allele-specific oligonucleotide assay (ASO), we also screened for the IVS10 mutation, one of the most common PAH gene mutations in Mediterranean countries. Forty-two percent of the PKU chromosomes analyzed bore the IVS10 mutation, although it was present in the heterozygous state in all cases. Our data show an important genetic heterogeneity at the PAH locus in the Mexican population, and report the genetic influence of the Spanish immigration to the American continent.

The study of dermal ridges in schizophrenia has been extensive, but only recently has fluctuating asymmetry been described. This study relates dermatoglyphic patterns with the specific positive and negative symptoms of the disease in 72 DSM-III-R defined schizophrenia and 72 normal unrelated ethnically matched controls. Schizophrenic subjects had significant lower ridge counts in both hands. Fluctuating asymmetry in the a-b ridge counts was significantly lower in schizophrenic subjects (0.50 vs 0.70, p0.05). The positive and negative symptom scale (PANSS) was used to determine symptom severity. Schizophrenics with predominantly negative symptoms showed significantly lower counts and higher fluctuating asymmetry than schizophrenics with positive symptoms. Our study showed findings congruent with the hypothesis that schizophrenia could be related to central nervous system developmental abnormalities.

Cognitive impairment is a prominent feature of schizophrenia that correlates with functional outcome. In the clinical practice and research, there is a need to count on brief, reliable and standardized instruments to evaluate the cognitive profile in psychiatric, geriatric and neurological patients. There are only a few standardized and validated instruments with the Hispanic population, so the adaptation and validation of instruments become a high relevance issue. The Brief Neuropsychological Test in Spanish (NEUROPSI) is a brief neuropsychological battery evaluating a wide spectrum of cognitive functions and standardized with Spanish speaking population according to age and educational level. The purpose of the present study was to determine the sensitivity and specificity of this instrument for its clinical use in patients with schizophrenia, as well as in distinct subtypes of schizophrenic patients: positive, negative and mixed.We studied a total sample of 60 subjects (30 patients with schizophrenia and 30 matched controls). Using the total score we found 87.5 % sensitivity and 92.8% specificity. A discriminant analysis using the 25 subtest scores of the NEUROPSI accurately classified 83.3 % of the sample. None of the control subjects was classified as patient.Classification by subtype showed 80 % of patients with negative symptoms, 90 % of patients with positive symptoms and 70 % of patients with mixed symptoms.The accurate diagnosis of cognitive dysfunction in schizophrenic patients could help in management as well as development of more specific pharmacological treatment for each schizophrenic subtype.

It has been proposed that some sociodemographic variables may predict violent behavior in schizophrenic patients. The aim of this study was to investigate the relationship of violent behavior with sociodemographic and clinical features in schizophrenic patients.We included 106 schizophrenic patients. Sociodemographic and clinical characteristics of each patient were recorded in a previously designed record. Violent behaviors were assessed with the Overt Aggression Scale (OAS).From the total sample, 49.1 % of the patients were classified as violent. Marital status, alcohol abuse, number of previous psychiatric hospitalizations and age of first hospitalization were predictive variables for violent behavior in schizophrenia.Predictive sociodemographic variables for violence in schizophrenia are easy to measure during the first interview with the patient and can be useful for the prevention of future violence.