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Although genes play a major role in the etiology of schizophrenia, no major genes involved in this disease have been identified. However, several genes with small effect have been reported, though inconsistently, to increase the risk for schizophrenia. Recently, the 5HT2A 2 allele (T102C polymorphism) was reported to be over-represented in patients with schizophrenia. Other reports have found an excess of allele 2(C) only in schizophrenic patients who are resistant to clozapine, not in those who respond to clozapine. In this study, the 5HT2A receptor allele 2 frequencies were compared between 2 groups of patients with schizophrenia (39 responders and 63 nonresponders) based on long-term outcome and response to typical neuroleptics. A control group of 90 healthy volunteers screened for mental disorders was also included. Genotype 2/2 tended to be more frequent in patients with schizophrenia with poor long-term outcome and poor response to typical neuroleptics (Bonferroni corrected p = 0.09). This difference was significant in men (Bonferroni corrected p = 0.054) but not in women. In addition, the age at first contact with psychiatric care was significantly younger in the patients with schizophrenia with genotype 2/2 than in patients with genotype 1/1. These result suggest that the 5HT2A-receptor gene may play a role in a subset of schizophrenia characterized by poor long-term outcome and poor response to neuroleptics.

10 male volunteers, right-handers, mean age 30.4 years, were recorded in four successive sequences: under 'eyes closed' conditions, right and then left hemisphere, followed by an 'eyes open' situation with visual attention fixed on a cartoon, right and then left hemisphere recordings. Each EEG recording was made simultaneously over 16 EEG channels for each hemisphere, according to a protocol previously described as well as Fourier analysis and EEG mapping on a minicomputer (HP 5451 C, HP 1000). Each EEG recording was stored on a cartography data base, and 90 maps could be drawn from 10 spectral parameters applied to the raw EEG and 5 frequency bands. Permutation paired Fisher tests were applied to three main EEG parameters: mean centroid frequencies, RMS amplitudes in microvolts and relative (%) amplitudes. Activation of EEG in the 'eyes open' situation during visual fixation was found compared to the 'eyes closed' situation: decreasing dominant EEG frequency and low delta and theta mean frequencies, no change in a mean alpha frequency; increasing fast mean beta frequencies, together with a major decrease in theta, alpha, beta 1 amplitudes, and a concomitant increase in raw EEG, delta and beta 2 amplitudes. Finally, the percent alpha amplitude was decreased when other percent amplitudes were increased in delta, theta, beta 1 and beta 2 frequency bands. A symmetry between hemispheres was observed in the 'eyes closed' situation. Averaged EEG maps between subjects illustrate these findings, especially relative (%) alpha amplitude maps and also maps of coefficients of resonance of the alpha rhythm.

RésuméUne hyperactivité de l’axe hypothalamo-hypophyso-cortico-surrénalien est souvent objectivée dans les dépressions majeures ou endogènes, particulièrement par le test de freinage à la dexaméthasone (DST).Certaines hypothèses évoquent un dysfonctionnement noradrénergique pour expliquer cette anomalie.Afin de rechercher les liens entre l’axe HPA et une anomalie du métabolisme de la noradrénaline (NA) cérébrale, 47 déprimés majeurs ont été étudiés.Pour chaque déprimé étaient mesurés l’excrétion urinaire du MHPG de 24 heures et un test de freinage à la dexaméthasone était effectué.Aucune corrélation n’est retrouvée entre l’âge et la sévérité de la dépression d’une part et d’autre part, l’excrétion du MHPG et les chiffres de cortisolémie pré et post dexaméthasone. Par contre, il existe une corrélation positive entre l’âge et l’excrétion du MHPG et entre l’âge et la cortisolémie post dexaméthasone, entre la durée du sevrage thérapeutique et la cortisolémie pré dexaméthasone et surtout, entre la cortisolémie pré DST et post DST.Aucune corrélation ne peut âtre retrouvée entre l’excrétion du MHPG et la cortisolémie maximale post dexaméthasone.Il n’y a pas de différence d’excrétion urinaire du MHPG entre les suppresseurs et les non suppresseurs qui sont au nombre de 19 (40 %).Lorsque les déprimés sont séparés en hauts excréteurs et bas excréteurs de MHPG, il existe une tendance significative des déprimés hauts excréteurs à présenter un pourcentage supérieur de non suppresseurs.L’étude ne confirme pas l’hypothèse hyponoradrénergique de l’échappement à la dexaméthasone. Elle tend plutôt à démontrer une association entre une hyperactivité de l’axe HPA et une excrétion urinaire élevée de MHPG.De nombreux facteurs peuvent peut-âtre expliquer les difficultés à mettre en évidence les liens entre l’échappement au freinage par la dexaméthasone et une anomalie du métabolisme de NA cérébrale lorsque des mesures biologiques périphériques sont utilisées.

The potential value of pretreatment urinary 3-methoxy, 4-hydroxyphenylethyleneglycol (MHPG) levels to predict the therapeutic response to antidepressants was studied by measuring urinary MHPG output in 42 depressed inpatients treated with a selective inhibitor of serotonin (Indalpine) or noradrenaline (Maprotiline) reuptake. Among the 42 depressed inpatients there were 33 cases of major depressive episode. Patients were treated for at least 3 weeks, firstly with intravenous infusions of maprotiline or indalpine which have been administered at random. No difference in pretreatment urinary MHPG levels was found between the responders to indalpine (1.08 +/- 0.48 micrograms/24 h/mg of creatinine) and the responders to maprotiline (1.15 +/- 0.62 micrograms/24 h/mg of creatinine). However, there was a difference in the pretreatment levels of urinary MHPG between the non-responders to indalpine (0.56 +/- 0.28 microgram/24 h/mg of creatinine) and the non-responders to maprotiline (1.37 +/- 0.68 micrograms/24 h/mg of creatinine). No correlation between this biochemical parameter and HDRS score was found. These results indicate that, in this study, there is no obvious relationship between the pretreatment urinary MHPG levels in depressed patients and their therapeutic response to specific inhibitors of noradrenaline or serotonin reuptake. However, there was a positive trend towards a lower pretreatment MHPG level to be associated with lack of response to indalpine.