Objectives: Was to evaluate the effect of different regional anesthetics (articaine with epinephrine versus prilocaine with felypressin) on stress in the extraction of impacted lower third molars in healthy subjects.Sutdy Desing: A prospective single-blind, split-mouth cross-over randomized study was designed, with a control group. The experimental group consisted of 24 otherwise healthy male volunteers, with two impacted lower third molars which were surgically extracted after inferior alveolar nerve block (regional anesthesia), with a fortnight's interval: the right using 4% articaine with 1:100.000 epinephrine, and the left 3% prilocaine with 1:1.850.000 felypressin. Patients were randomized for the first surgical procedure. To analyze the variation in four stress markers, homovanillic acid, 3-methoxy-4-hydroxyphenylglycol, prolactin and cortisol, 10-mL blood samples were obtained at t = 0, 5, 60, and 120 minutes. The control group consisted of 12 healthy volunteers, who did not undergo either extractions or anesthetic procedures but from whom blood samples were collected and analyzed in the same way.Results: Plasma cortisol increased in the experimental group (multiple range test, P<0.05), the levels being significantly higher in the group receiving 3% prilocaine with 1:1.850,000 felypressin (signed rank test, p<0.0007). There was a significant reduction in homovanillic acid over time in both groups (multiple range test, P<0.05). No significant differences were observed in homovanillic acid, 3-methoxy-4-hydroxyphenylglycol or prolactin concentrations between the experimental and control groups.Conclusions: The effect of regional anesthesia on stress is lower when 4% articaine with 1:100,000 epinephrine is used in this surgical procedure.

Introduction Certain personality traits and genetic polymorphisms are contributing factors to bipolar disorder and its symptomatology, and in turn, this syndrome influences personality. The aim of the present study is to compare the personality traits of euthymic bipolar patients with healthy controls and to investigate the effect of the catechol-O-methyltransferase (COMT) Val158Met genotype on those traits. We recruited thirty seven bipolar I patients in euthymic state following a manic episode and thirty healthy controls and evaluated their personality by means of the Cloninger’s Temperament and Character Inventory (version TCI-R-140). We assessed the influence of the polymorphism Val158Met in the COMT gene on the personality of these patients. The patients scored higher than controls in harm avoidance (61.3±12.5 vs. 55.3±8.1) and self-transcendence (45.3±12.8 vs. 32.7±8.2) and scored lower than controls in self-directedness (68.8±13.3 vs. 79.3±8.1), cooperativeness (77.1±9.1 vs. 83.9±6.5) and persistence (60.4±15.1 vs. 67.1±8.9). The novelty seeking dimension associates with the Val158Met COMT genotype; patients with the low catabolic activity genotype, Met/Met, show a higher score than those with the high catabolic activity genotype, Val/Val. Conclusions Suffering from bipolar disorder could have an impact on personality. A greater value in harm avoidance may be a genetic marker for a vulnerability to the development of a psychiatric disorder, but not bipolar disorder particularly, while a low value in persistence may characterize affective disorders or a subgroup of bipolar patients. The association between novelty seeking scores and COMT genotype may be linked with the role dopamine plays in the brain’s reward circuits.

The Val108/158Met polymorphism of the catechol-O-methyltransferase gene (COMT) is known to interact with the function of various neuroreceptor systems in the brain. We have recently shown by post-mortem receptor autoradiography that the number of mu-opioid (MOP) receptor binding sites depends on the number of COMT Met108/158 alleles in distinct human brain regions. We now investigated COMT Val108/158Met related levels of the MOP receptor protein and its endogenous ligands met-enkephalin and beta-endorphin in the human frontal cortex, thalamus and basal ganglia. Semiquantitative immunostaining and in situ hybridization were applied in a cohort of 17 human brain tissues from healthy donors. MOP receptor protein levels paralleled previous ligand binding results with a significantly higher MOP receptor expression in the mediodorsal nucleus of the thalamus of COMT Met108/158 allele carriers. Also met-enkephalin peptide levels correlated with the genotype in this structure, with the lowest expression in COMT Met108/158 homozygous individuals. Beta-endorphin was not detectable in the cortex, basal ganglia or thalamus, and therefore is unlikely to contribute to changes of the MOP receptor system. These results confirm the impact of the COMT Val108/158Met polymorphism on the MOP receptor system and may support the hypothesis of an enkephalin related turnover of MOP receptors at least in some brain structures.

IntroductionMany authors support the idea that Mood Incongruent Psychosis is a subtype of affective illness, although no clear definition or etiopathogenic basis of the congruent or incongruent subtype has been found.AimsIn this study we intend to evaluate clinical and biological differences between Psychotic Bipolar I patients who have mood congruent or mood incongruent psychotic symptoms.MethodsThe study has been carried out in 80 Psychotic Bipolar I Patients before, and after, four weeks of treatment with Olanzapine plus Lithium. We studied the correlation between the plasma concentration, before treatment, of the dopamine metabolite 3,4 Dihydroxyphenylacetic acid (DOPAC) and the clinical response to treatment.ResultsThe most remarkable result found was that Clinical Improvement after 28 days of treatment correlated positively with the initial concentration of DOPAC, but ONLY in the subgroup of patients with congruent psychotic symptoms.ConclusionsFrom our results it seems that the Congruence and Incongruence of psychosis in bipolar I patients can provide a basis to objectively divide these patients. Both groups can be distinguished based on the relationship established between their concentration of DOPAC before treatment and their clinical response to the pharmacological treatment.Supported byUniversidad del País Vasco Grant N° EHU 09/21 and Fondo de Investigación Sanitaria and Feder Founds Grant N° 09/01760.

In the present study we have measured, on a monthly basis, the concentration of plasma homovanillic acid (pHVA) in schizophrenic patients during 13 months of their pharmacological treatment. The average pHVA values of each patient were within the range of 7.30–17.70 ng/ml and the coefficients of variation for each patient (CV %) were within the range of 13–33%. Half of the patients that showed higher pHVA CV% values also showed higher scores on the Brief Psychiatric Rating Scale at the beginning of the study, and improved more after 6 months, when compared to the remaining 50% with lower CV% values. There was no significant relationship between the scores of the Wisconsin Card Sort Test and the concentration or the CV% of the pHVA of each patient. A greater variability in the pHVA may be associated with a greater plasticity of the dopaminergic system and a better clinical response.

Metabolites of dopamine and norepinephrine measured in the plasma have long been associated with symptomatic severity and response to treatment in schizophrenic, bipolar and other psychiatric patients. Plasma concentrations of catecholamine metabolites are genetically regulated. The genes encoding enzymes that are involved in the synthesis and degradation of these monoamines are candidate targets for this genetic regulation. We have studied the relationship between the Val158Met polymorphism in catechol O-methyltransferase gene, variable tandem repeat polymorphisms in the monoamine oxidase A gene promoter, and plasma concentrations of 3-methoxy-4-hydroxyphenylglycol, 3,4-dihydroxyphenylacetic acid and homovanillic acid in healthy control subjects as well as in untreated schizophrenic and bipolar patients. We found that the Val158Met substitution in catechol O-methyltransferase gene influences the plasma concentrations of homovanillic and 3,4-dihydroxyphenylacetic acids. Although higher concentrations of plasma homovanillic acid were found in the high-activity ValVal genotype, this mutation did not affect the plasma concentration of 3-methoxy-4-hydroxyphenylglycol. 3,4-dihydroxyphenylacetic acid concentrations were higher in the low-activity MetMet genotype. Interestingly, plasma values 3-methoxy-4-hydroxyphenylglycol were greater in schizophrenic patients and in bipolar patients than in healthy controls. Our results are compatible with the previously reported effect of the Val158Met polymorphism on catechol O-methyltransferase enzymatic activity. Thus, our results suggest that this polymorphism, alone or associated with other polymorphisms, could have an important role in the genetic control of monoamine concentration and its metabolites.

It has been suggested that the family history of psychotic disorders is useful in defining homogeneous groups of bipolar patients. The plasma homovanillic acid (pHVA) concentrations have been related to the effect of antipsychotic treatment in psychotic patients. We have studied the influence of a positive family history of psychotic disorders both on the variation of pHVA levels and on the relation between pHVA concentrations and the clinical response to treatment. Clinical status and pHVA levels were assessed in 58 medication free patients before and after 4 weeks of treatment with olanzapine and lithium. Clinical improvement correlated positively with pHVA levels on the 28th day of treatment only in the patients having first degree relatives with psychotic disorders. The pHVA levels did not decrease after 28 days of treatment. Our results reinforce the idea that a positive family history of psychosis in psychotic bipolar disorders may constitute a good basis for sub-grouping these patients.

We have determined the plasma (p) concentration of gamma-aminobutyric acid (GABA) and the dopamine metabolite homovanillic acid (HVA), and the pHVA/pGABA ratio in schizophrenic and bipolar patients. The research was undertaken in a geographic area with an ethnically homogeneous population. The HVA plasma concentrations were significantly elevated in the schizophrenic patients compared to the bipolar patients. The levels of pGABA was significantly lower in the two groups of patients compared to the control group, while the pHVA/pGABA ratio was significantly greater in the both groups of patients compared to the controls. As the levels of pHVA and pGABA are partially under genetic control it is better to compare their concentrations within an homogeneous population. The values of the ratio pHVA/pGABA are compatible with the idea of an abnormal dopamine-GABA interaction in schizophrenic and bipolar patients. The pHVA/pGABA ratio may be a good peripheral marker in psychiatric research.

We examined the catechol-O-methyl transferase (COMT) Val108/158Met genotype in 160 type 1 bipolar patients. We also analyzed the plasma concentrations of homovanillic acid (HVA), 3-methoxy-4-hydroxyphenylethylenglycol (MHPG) and 3,4-dihydroxyphenylacetic acid in 60 of those patients who had been without mood stabilizers or neuroleptic treatment for at least 8 days. Results: Patients with congruent psychotic symptoms presented a higher plasma concentration of HVA than mood incongruent psychotic patients. The Val/Val genotype was associated with higher plasma concentrations of HVA and MHPG. We detected a larger proportion of patients with psychotic symptoms in the Val/Val genotype group, although this did not reach statistical significance. It was found that the distribution of the COMT genotype was not influenced by the congruent/incongruent nature of the psychotic symptoms. Limitations: The proportion of patients without psychotic symptoms in our sample was low. This fact limits the value of some comparisons. Conclusions: Congruent and incongruent psychotic patients can be distinguished in terms of the concentration of plasma HVA. Based on the presence or absence of mood incongruent symptoms, the Val108/158Met polymorphism of the COMT gene alone does not appear to be a crucial determinant in the division of psychotic bipolar patients. Nevertheless, COMT polymorphisms may influence some of the characteristics of the patients by their effect on monoamine metabolism.

Presentamos un resumen de la discusion de los resultados mas relevantes de un trabajo que tiene como objetivo la busqueda de marcadores geneticos y neuroquimicos, en relacion a diferentes subtipos de pacientes bipolares tipo I. Los pacientes ingresaron en la Unidad de Hospitalizacion de Corta Estancia del Hospital Psiquiatrico de Zamudio.

President of the IPEG and of the Scientific Program Committee Gé S.F. Ruigt, Oss (The Netherlands) President of the Local Organizing Committee Rémy Luthringer, Rouffach (France)

The relation between changes in the levels of plasma homovanillic acid (pHVA) and clinical evolution during neuroleptic treatment of schizophrenic patients has not been satisfactorily characterized, as a number of conflicting findings have been reported. Significant correlations have generally been found using the assessment of positive symptoms as an index of clinical outcome. Nevertheless, attempts to correlate pHVA concentrations with negative symptoms have yielded contradictory results. With a view to evaluating if different responses in negative symptoms are associated with distinct pHVA profiles, we examined the levels of pHVA in 46 neuroleptic-free schizophrenic patients and in these patients after neuroleptic treatment. Negative and positive symptoms were also addressed before and after treatment. Our results reveal that at least two classes of negative symptoms exist; the clinical evolution of the first class of negative symptoms parallels that of positive symptoms, and clinical improvement correlates with reduced dopaminergic activity. In contrast, in the second class, reduced dopaminergic activity is associated with a further deterioration of negative symptoms. These findings corroborate the heterogeneity of negative symptoms and may contribute to a better definition of endophenotypes in the schizophrenic syndrome.

Las concentraciones de ciertos metabolitos, como expresion de ciertos genes y como respuesta al entorno significarian un anadido conveniente para estudiar simultaneamente en cada paciente un elevado numero de caracteristicas biologicas geneticamente condicionadas y poder asi definir objetivamente subgrupos de pacientes. Finalmente, se podrian encontrar tratamientos farmacologicos personalizados que garantizasen una mayor eficacia terapeutica.

SUMMARY After a few words about the concept of homeostasis, we present some considerations related to the mechanisms that maintain mental stability. Particular emphasis is given to a brain restitutive system that is dopamine dependent. And some considerations are made about the modern formulation of the dopaminergic hypotheis of psychotic destabilization.