José Guimón

Catechol O-methyltransferase and monoamine oxidase A genotypes, and plasma catecholamine metabolites in bipolar and schizophrenic patients.

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.

GABA and Homovanillic Acid in the Plasma of Schizophrenic and Bipolar I 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.

Prejudice and Realities in Stigma

The negative attitudes toward mental illness can be based not only on ignorance and intolerance but also on such real factors as dangerousness, unpredictability, disability, and the burden the psychiatric patient represents for the community, particularly for members of the family and professionals who experience the stress that results from caring for them. A lack of access to health services can be due to discrimination or social stigma, such as in the case of chronic mental patients. However, other patients—anxious, shy, fearful, avoidant, obsessional, schizoid and other—whose behavioral difficulties also remain frequently undetected as the public can find it very difficult to overcome the barriers that society poses to obtain some services, privileges, and compensations. They are, in fact, indirectly discriminated. Questions concerning the relation between mental health and human rights are summarily addressed in some documents of international organizations, particularly, the UN Principles for the Protection of Persons with Mental Illness and the Improvement of Mental Health Care. However, many situations of inequity in relation to psychiatric care are detected in contemporary systems of managed care, but solutions are not easy to implement. If we treat disabled people as equal in dignity and right, differences in physical or mental capability among people should be accommodated without discrimination. This equal treatment requires a combination of psychological approaches such as modifications in public attitudes toward disabled people and social efforts to confront the concrete realities of disability and legal measures (including positive discrimination) when the previous steps are not sufficient.

Biological Correlates of the Congruence and Incongruence of Psychotic Symptoms in Patients with Type 1 Bipolar Disorder

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.

Plasma homovanillic acid and family history of psychotic disorders in bipolar I patients

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.

Decaffeinated therapeutic communities

Over the last 35 years we have developed a number of group therapy programs with an orientation toward community therapy. In the last 20 years, even though at certain centers we have maintained a milieu therapy focus, the programs have become less psychodynamic and less democratic – somewhat ‘decaffeinated’, in fact. This, however, does not mean they are less efficient from the point of view of dynamics, because our experience over the years has, in fact, shown the negative effects of the caffeine administered by certain lines of psychoanalytic action and ‘pseudo-democratic’ environments. Many people now consume ‘light’ products and drink decaffeinated coffee on medical advice, and this is what we have decided to do at our centers as we try to illustrate in this article.

P01-191 - Biological support to distinguish between congruent and incongruent symptoms in psychotic bipolar i patients

Introduction Many 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. Aims In this study we intend to evaluate clinical and biological differences between Psychotic Bipolar I patients who have mood congruent or mood incongruent psychotic symptoms. Methods The 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. Results The 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. Conclusions From 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 by Universidad del Pais Vasco Grant N° EHU 09/21 and Fondo de Investigacion Sanitaria and Feder Founds Grant N° 09/01760.

Efecto paradójico del tratamiento con aripiprazol en un paciente bipolar: de la psicofarmacología a la psicopatología

El trastorno bipolar es una enfermedad cronica, caracterizada por remisiones y exacerbaciones, cuya evolucion puede modificarse favorablemente con un tratamiento apropiado. Aunque el tratamiento de los episodios agudos es importante, la prevencion de recaidas mediante un tratamiento de mantenimiento es el objetivo terapeutico principal. Se ha estimado que aproximadamente el 60% de la poblacion diagnosticada de trastorno bipolar I experimenta de forma cronica dificultades en la actividad sociolaboral. Los sintomas subclinicos entre los episodios agudos son, en un gran numero de pacientes, la causa de esas dificultades. Presentamos el caso de una paciente con subsintomas interepisodicos, a la que instauramos un tratamiento con aripiprazol. Este neuroleptico, de singular mecanismo de accion, ha producido en nuestra paciente sorprendentes consecuencias clinicas de interesante discussion.

P03-48 Agression in a dynamically oriented crisis unit. Management and evolution

Acute episodes are treated in AMSA psychiatric services in a emergency service including a call center, domicilliary visits, a crisis unit, three short-term day hospitals and a short-term stay unit in a general hospital. An Intensive Brief Dynamic Group Therapy is offered in the units allowing for a decreased appearance of self and hetero aggression in patients both during the crisis and after one year as shown in a follow-up study.

Subgroups in training communities

Over the past thirty years we have developed a number of group therapy programmes, involving many severely ill patients, with an orientation towards community therapy, in a dozen different care units (short-stay units in general hospitals, rehabilitation units and day hospitals) in Spain and in Switzerland. In these alternative units for severely ill patients, group analysis, with its particular emphasis on the ‘here and now’ and on inter-member cohesiveness, has shown itself to be, in our experience, a useful stabilizing (‘buffer’) tool, fostering involvement and support and allowing a controlled expression of anger and aggressiveness. These programmes (which we have termed ‘decaffeinated therapeutic communities’) include, as a minimum: a daily group of ‘medium size’, bringing together patients and staff; a ‘small group’ of patients, with a dynamic orientation, but with occasional cognitive-behavioural techniques and several group activities (‘group work’, in the Foulkes sense). In order to offer the professionals a ‘didactic setting’ with a ‘therapeutic community’ orientation, thirty years ago we developed a programme for interdisciplinary training for those working in such care units (psychiatrists, nurses and psychosocial workers). The course was run over several seminars each lasting four days, and each including small groups, large groups, a section on theory and group supervision. Over 1,500 professionals working in these units have undergone this kind of training. Our training organization has slowly developed through an institution in the sense of Kaës (2000a), who uses it to refer to the set of rules, regulations and activities grouped around social values and functions. This paper describes the appearance of two or more conflicting subgroups. Subgrouping can have a disruptive effect on these organizations, but, if the goals of the subgroup are coherent with the goals of the parent organization, subgrouping may ultimately enhance group cohesiveness.