Marcadores biologicos en Psiquiatria / Biological markers in Psychiatry

In order to determine wheter psycopathology is associated with charactheristic neurochemical changes of psychiatric patients, Noradrenergic; Dopaminergic and Serotoninergic urine compounds were quantified in 50 patients (32 females and 18 males) between 20 and 60 years old. They were classified in four groups, according to DSM-IV criteria; in MAJOR DEPRESSION (MD) 30 cases, OBSESSIVE COMPULSIVE DISEASE (OCD) 9 cases, BIPOLAR DEPRESSION (BD)4 cases and SCHIZOPHRENIA (SZ) 7 cases. The following Amine metabolites were determined in 24 hours urine samples Phenylethilamine (PEA); 3-Metho-4-Hidroxy Phenilglycol (MHPG); 5-Hidroxy-indol acetic acid (5HIAA) Homovanilic acid (HVM); Bufotenine (BU); Ometil Bufotenine (OMBU) and 3-5 Metoxy-NN-Dymethyltryptamine (MNNDMT). The results showed a dicrease of Pea levels in 43 per cent of DM; 33 per cent of OCD; 25 per cent of BP and 42 per cent SZ. MOPEG levels were disminished in 53 per cent of DM; 66 per cent of OCD; 25 per cent of BP and 85 per cent of SZ. There was an increase of HVM levels in 10 per cent of DM; 11 per cent of OCD and 25 per cent of BP. There was a dicrease of 5-HIAA levels in 10 per cent of DM while it was increased in 33 per cent and 14 per cent of SZ, BU, OMBU and NNDMT were positive in 71 per cent of SZ; 46 per cent of DM; 55 per cent of OCD and 50 per cent of BP. Our findings are consistent with the hypothesis that PEA; MHPG; 5-HIAA and HVM compounds could be "State markers"of DM and HVM of BP and SZ patients. There is further evidence to support a close interrelationship between the three systems and the urinary excretion of methylates compounds specially in SZ and in DM, OCD and BP patients.

[Treatment of patients with panic disorder and an elevated urinary excretion of MHPG using imipramine or clonazepam]. / Tratamiento de pacientes con trastorno de pánico y elevada excreción urinaria de MHPG con imipramina o clonazepam.

The response to treatment with imipramine or clonazepam was evaluated in patients with panic disorder. These patients had a high urinary 3-methoxy-4-hydroxy-phenylglycol 24 h-excretion and normal plasma lactate levels. Both drugs were efficient as anti-panic agents, but clonazepam resulted more efficacious than imipramine by the scores of Hamilton Anxiety or Depression Scales. Moreover, clonazepam also reduced the anticipatory anxiety.

Biochemical correlate of depression in children.

The degree of depression in 88 abandoned children was analysed through a depression rating scale adapted to prepubertal children. The items were grouped into three dimensions: sociological-relational, psychological and biological. In 46 children from this sample it was dosed plasmatic cortisol and the urinary excretion of catecholamine, VMA, HVA and 5-HIAA. When analysing the principal components, the sociological and psychological dimensions were the most important ones in the sample, followed by age and catecholamine variables. The group of male depressed children presented a higher level of catecholamine urinary excretion and a lower peak of plasmatic cortisol than the non-depressed group. The variable age, in both sexes, was correlated with the biochemical variable catecholamine. Biochemical alterations are present in depressed children but it is difficult to show a correlation of dependence between them and the phenomenological aspects of depression.

Biochemical correlate of depression in children

O grau de depressäo em 88 crianças abandonadas foi analisado por escala de avaliaçäo de depressäo adaptada para crianças na pré-puberdade. Os itens da escala foram agrupados em três dimensöes: sociológico-relacional, psicológica e biológica. Em 46 crianças desta amostra foram dosados o cortisol plasmático e a excreçäo urinária de catecolomina, VMA, HVA e 5-HIAA. Pela análise dos principais componentes, mostraram-se mais importantes, na amostra, as dimensöes sociológica e psicológica, seguidas dos componentes idade e catecolomina. O grupo de crianças do sexo masculino com depressäo apresentava maior nível de excreçäo urinária de catecolomina e menor pico de cortisol plasmático que o grupo sem depressäo. A variável idade, em ambos os sexos, correlacionava-se à variável catecolomina. Alteraçöes bioquímicas estäo presentes em crianças com depressäo, mas é difícil demonstrar correlaçäo de dependência entre elas e aspectos fenomenológicos da depressäo

[Review and updating of the diagnostic sensibility of the dexamethasone suppression test and urinary determination of phenylethylamine and 3-methoxy-4-hydroxyphenylethylglycol in the diagnosis of endogenous depression]. / Revisión y actualización de la sensibilidad diagnóstica del test de la supresión de la dexametasona y de la determinación de feniletilamina y ácido 3-metoxi-4-hidroxi-feniletilglicol urinarios en el diagnóstico de la depresión endógena.

60 endogenous depressive patients (DSM III: 296.2x, 3x, 296.5x) were studied according to the following diagnostic techniques: DST (Carroll's standardization), Phenyl-ethyl-amine (PEA) urinary quantification (Spatz's technique) and 3-Methoxy-4-Hydroxyphenylethyl Glycol (MHPG) urinary quantification (Bigelow's technique). Seven groups were thus obtained according to their being positive in, at least, one of those determinations. The above mentioned techniques allow the finest of discriminations since 5% of the patients only kept undetected. The critical path analysis to this conclusion is discussed.

Revisión y actualización de la sensibilidad diagnóstica del test de la supresión de la dexametasona y de la determinación de feniletilamina y ácido 3-metoxi-4-hidroxi-feniletilglicol urinários en el diagnóstico de la depresión endógena / Review and updating of the diagnostic sensibility of the dexamethazone suppression test and urinary determination of phenylethylamine and 3-methoxy-4-hydroxyphenylglycol in the diagnosis of endogenous depression

Se estudian sesenta pacientes depresivos endógenos (DSM III: 296.2x, 3x y 296.5x) con las siguientes técnicas diagnósticas: DST (Standarization de Carroll), la cuantificación (u) de FEA (Técnica de Spatz) y la cuantificación (u) de MOPEG (Técnica de Bigelow). Se obtienen siete subgrupos, según resulten positivos por lo menos en una de las determinaciones. Se observa una gran sensibilidad al utilizar las tres técnicas, pues sólo un 5% de los pacientes no es detectado. Se discute el camino crítico que conduce a estas conclusiones

Revisión y actualización de la sensibilidad diagnóstica del test de la supresión de la dexametasona y de la determinación de feniletilamina y ácido 3-metoxi-4-hidroxi-feniletilglicol urinários en el diagnóstico de la depresión endógena / Review and updating of the diagnostic sensibility of the dexamethazone suppression test and urinary determination of phenylethylamine and 3-methoxy-4-hydroxyphenylglycol in the diagnosis of endogenous depression

Se estudian sesenta pacientes depresivos endógenos (DSM III: 296.2x, 3x y 296.5x) con las siguientes técnicas diagnósticas: DST (Standarization de Carroll), la cuantificación (u) de FEA (Técnica de Spatz) y la cuantificación (u) de MOPEG (Técnica de Bigelow). Se obtienen siete subgrupos, según resulten positivos por lo menos en una de las determinaciones. Se observa una gran sensibilidad al utilizar las tres técnicas, pues sólo un 5% de los pacientes no es detectado. Se discute el camino crítico que conduce a estas conclusiones (AU)

[In search of biological markers of affective disorders]. / En busca de marcadores biológicos de trastornos afectivos.

The field of biological markers of affective disorders is defined on its conceptual and methodological basis, and the results of some studies in this area conducted at the Mexican Institute of Psychiatry are reported. Urinary MHPG levels greater than 2800 micrograms/24 hs, suggest a poor response to conventional drug treatment. Allnight EEG recordings, showed that sleep architecture of depressed patients is substantially different from that of normal subjects; particularly REM sleep latency, which can reliably discriminate between patients and controls. The dexamethasone suppression test showed a diagnostic confidence of 77% which is similar to that reported from other centers. The author suggests caution on interpreting these results, as further prospective longitudinal studies are needed before firm conclusions can be drawn.

En busca de Marcadores biológicos de trastornos afectivos / Searching biological Markess of offective disorders

Se revisan algunos aspectos teóricos y metodológicos en relación a los marcadores biológicos de transtornos afectivos, y se presentan los resultados de la experiencia acumulada en este campo en el Instituto Mexicano de Psiquiatría. Niveles de MHPG urinario > 2800 ug/24 hs, sugieren pocas posibilidades de respuesta al tratamiento farmacológico convencional. El registro polisomnográfico muestra cambios sustanciales en la arquitectura del sueño de los enfermos deprimidos, siendo el acortamiento de la latencia al primer sueño MOR, el que mejor premite distinguirlos de los sujetos sanos. La puebra de supresión con dexametasona, tuvo una confianza diagnóstica del 77%, equiparable a la reportada en otros centros

En busca de Marcadores biológicos de trastornos afectivos / Searching biological Markess of offective disorders

Se revisan algunos aspectos teóricos y metodológicos en relación a los marcadores biológicos de transtornos afectivos, y se presentan los resultados de la experiencia acumulada en este campo en el Instituto Mexicano de Psiquiatría. Niveles de MHPG urinario > 2800 ug/24 hs, sugieren pocas posibilidades de respuesta al tratamiento farmacológico convencional. El registro polisomnográfico muestra cambios sustanciales en la arquitectura del sueño de los enfermos deprimidos, siendo el acortamiento de la latencia al primer sueño MOR, el que mejor premite distinguirlos de los sujetos sanos. La puebra de supresión con dexametasona, tuvo una confianza diagnóstica del 77%, equiparable a la reportada en otros centros (AU)

Dopamine-norepinephrine interaction in hyperactive boys treated with d-amphetamine.

We studied the relationship between the excretion of 3-methoxy-4-hydroxyphenylglycol, the main metabolite of central nervous system norepinephrine, and homovanillic acid, the main metabolite of dopamine, in 16 hyperactive boys and ten controls who were admitted to a clinical research center. We further examined the effect of d-amphetamine (0.5 mg/kg body weight daily for two weeks) on that relationship. The correlation coefficients r between MHPG and HVA excretion were significantly negative in hyperactive boys and significantly positive in controls when the relational effects of age, body surface, and 24-hour urinary creatinine with MHPG and HVA excretion were removed. Furthermore, the correlation coefficient r in hyperactive boys and in responders at baseline differed significantly from the correlation coefficients in post-treatment and in controls. The post-treatment correlation coefficient in hyperactive boys and responders did not differ from that in controls. We suggest an altered relationship between DA and NE activity in hyperactive children. Meaningful interpretation of the data should await the availability of more information on the amount of contribution of central NE and DA metabolism to urinary MHPG and HVA in both hyperactive and normal children.

[Clinical, biochemical and psychopharmacologic correlates in patients with depressive symptomatology]. / Correlato clínico, bioquímico y psicofarmacológico en pacientes con sintomatología depresiva.

A population of 41 clinic outpatients suffering depressive symptomatology was studied. According to the presence or absense of sixteen specific symptoms it was possible to distribute these patients in three different groups. Simultaneously urinary determinations of phenethylamine (PEA), 3-methoxy-4-hydroxyphenylethylglicol (MHPG), phenylacetic acid, 5-hydroxyindolacetic acid and serum 5-hydroxytriptamine were performed. A clossed clinical-biochemical correlation was noted in each group in relation to PEA and MHPG daily output. The other determinated values were not significant. Besides the clinical data, the mentioned groups presented the following characteristic output data: group A: decreased PEA and MHPG levels, group B, decreased PEA and normal MHPG levels and group C: normal values of the two substances. Five tricyclic antidepressant drugs were tested in the three groups. It was shown that patients with low pretreatment urinary output values of PEA and MHPG responded favourably to imipramine, desipramine and nortriptyline, alone or in association. On the other side, the group B responded favourably to chlorimipramine and amitriptiline, alone or in combination. No change or clinically worse were observed in patients of these groups when medication was not administrated according to the described form. The group with normal PEA and MHPG output values worsened or did not respond to medication following administration of any of the antidepressants essayed. Only psychotherapeutic treatment in combination with ansiolitics let to an improvement of symptomatology. At least, our findings suggest a closed clinical-biochemical-psychopharmacological correlate of some classes of depression that may provide rational basis for a more predictive tricyclic antidepressant therapy.

Norepinephrine metabolism and clinical response to dextroamphetamine in hyperactive boys.

The 24-hour urinary catecholamine metabolites 3-methoxy-4-hydroxyphenylglycol, normetanephrine, and metanephrine were measured in 23 hyperactive boys and 13 matched healthy controls. The hyperactive children excreted lower MHPG and higher NM (low MHPG/NM ratio) amounts than in controls. The administration of d-amphetamine in the dose of 0.5 mg/kg body weight divided over two doses daily for two weeks decreased MHPG excretion in the hyperactive children. When the hyperactive children group was divided into drug responders and nonresponders according to their pre- and post-treatment scores on the Conners Teacher Questionnaire, d-amphetamine administration decreased MHPG excretion in the responders and did not change it in the nonresponders. Percent decrease in MHPG excretion correlated significantly with percent change in the hyperactivity factor of the questionnaire on the Spearman Rank Order Correlation Coefficient. Pretreatment urinary metabolites did not differentiate the responders from nonresponders. It is suggested that a relationship between CNS norepinephrine metabolism and hyperactivity exists and that d-amphetamine may achieve its therapeutic action in hyperactive children by altering CNS NE metabolism.