Bypassing use-dependent plasticity in the primary motor cortex to preserve adaptive behavior.

Behavioral adaptation, a central feature of voluntary movement, is known to rely on top-down cognitive control. For example, the conflict-adaptation effect on tasks such as the Stroop task leads to better performance (e.g. shorter reaction time) for incongruent trials following an already incongruent one. The role of higher-order cortices in such between-trial adjustments is well documented, however, a specific involvement of the primary motor cortex (M1) has seldom been questioned. Here we studied changes in corticospinal excitability associated with the conflict-adaptation process. For this, we used single-pulse transcranial-magnetic stimulation (TMS) applied between two consecutive trials in an interference flanker task, while measuring motor-evoked potentials (MEPs) after agonistic and antagonistic voluntary movements. In agonist movement, MEP amplitude was modulated by recent movement history with an increase favoring movement repetition, but no significant change in MEP size was observed whether a previous trial was incongruent or congruent. Critically, for an antagonist movement, the relative size of MEPs following incongruent trials correlated positively with the strength of behavioral adaptation measured as the degree of RT shortening across subjects. This post-conflict increase in corticospinal excitability related to antagonist muscle recruitment could compensate for a potential deleterious bias due to recent movement history that favors the last executed action. Namely, it prepares the motor system to rapidly adapt to a changing and unpredictable context by equalizing the preparation for all possible motor responses.

Striatal dopamine mediates hallucination-like perception in mice.

Hallucinations, a central symptom of psychotic disorders, are attributed to excessive dopamine in the brain. However, the neural circuit mechanisms by which dopamine produces hallucinations remain elusive, largely because hallucinations have been challenging to study in model organisms. We developed a task to quantify hallucination-like perception in mice. Hallucination-like percepts, defined as high-confidence false detections, increased after hallucination-related manipulations in mice and correlated with self-reported hallucinations in humans. Hallucination-like percepts were preceded by elevated striatal dopamine levels, could be induced by optogenetic stimulation of mesostriatal dopamine neurons, and could be reversed by the antipsychotic drug haloperidol. These findings reveal a causal role for dopamine-dependent striatal circuits in hallucination-like perception and open new avenues to develop circuit-based treatments for psychotic disorders.

Multiple controls exerted by 5-HT2C receptors upon basal ganglia function: from physiology to pathophysiology.

Serotonin2C (5-HT2C) receptors are expressed in the basal ganglia, a group of subcortical structures involved in the control of motor behaviour, mood and cognition. These receptors are mediating the effects of 5-HT throughout different brain areas via projections originating from midbrain raphe nuclei. A growing interest has been focusing on the function of 5-HT2C receptors in the basal ganglia because they may be involved in various diseases of basal ganglia function notably those associated with chronic impairment of dopaminergic transmission. 5-HT2C receptors act on numerous types of neurons in the basal ganglia, including dopaminergic, GABAergic, glutamatergic or cholinergic cells. Perhaps inherent to their peculiar molecular properties, the modality of controls exerted by 5-HT2C receptors over these cell populations can be phasic, tonic (dependent on the 5-HT tone) or constitutive (a spontaneous activity without the presence of the ligand). These controls are functionally organized in the basal ganglia: they are mainly localized in the input structures and preferentially distributed in the limbic/associative territories of the basal ganglia. The nature of these controls is modified in neuropsychiatric conditions such as Parkinson's disease, tardive dyskinesia or addiction. Most of the available data indicate that the function of 5-HT2C receptor is enhanced in cases of chronic alterations of dopamine neurotransmission. The review illustrates that 5-HT2C receptors play a role in maintaining continuous controls over the basal ganglia via multiple diverse actions. We will discuss their interest for treatments aimed at ameliorating current pharmacotherapies in schizophrenia, Parkinson's disease or drugs abuse.

Improvement of neurobehavioral disorders in children supplemented with magnesium-vitamin B6. I. Attention deficit hyperactivity disorders.

Some previous studies have reported the involvement of magnesium (Mg) deficiency in children with ADHD syndrome. In this work, 40 children with clinical symptoms of ADHD were followed clinically and biologically during a magnesium-vitamin B6 (Mg-B6) regimen (6 mg/kg/d Mg, 0.6 mg/kg/d vit-B6) which was set up for at least 8 weeks. Symptoms of ADHD (hyperactivity, hyperemotivity/ aggressiveness, lack of attention at school) were scored (0-4) at different times; in parallel, intraerythrocyte Mg2+ (Erc-Mg) and blood ionized Ca2+ (i-Ca) were measured. Children from the ADHD group showed significantly lower Erc-Mg values than control children (n = 36). In almost all cases of ADHD, Mg-B6 regimen for at least two months significantly modified the clinical symptoms of the disease: namely, hyperactivity and hyperemotivity/aggressiveness were reduced, school attention was improved. In parallel, the Mg-B6 regimen led to a significant increase in Erc-Mg values. When the Mg-B6 treatment was stopped, clinical symptoms of the disease reappeared in few weeks together with a decrease in Erc-Mg values. This study brings additional information about the therapeutic role of a Mg-B6 regimen in children with ADHD symptoms.

Improvement of neurobehavioral disorders in children supplemented with magnesium-vitamin B6. II. Pervasive developmental disorder-autism.

Previous studies reported positive results with the use of Mg-vitamin B6 in autism. Despite these reports, this intervention remains controversial. In order to study relationships between changes in clinical symtoms and biological parameters, 33 children (mean age: 4 [1-10] years old) with clinical symptoms of pervasive developmental disorder or autism (PDD, as defined in DSM-IV) were followed for at least 6 months; another group of 36 children (same age) devoided of any known pathology was used as control. All PDD children received a magnesium-vit B6 (Mg-B6) regimen (6 mg/kg/d Mg and 0.6 mg/kg/d vit B6). Intraerythrocyte Mg2+ (Erc-Mg), serum Mg2+ (s-Mg) and blood ionized Ca2+ (i-Ca) were measured before and after treatment. Clinical symptoms of PDD were scored (0 to 4). In contrast to s-Mg or i-Ca, PDD children exhibited significantly lower Erc-Mg values than controls (2.17 +/- 0.4 versus 2.73 +/- 0.23 mmol/L; 16/33). The Mg-B6 regimen led to an increase in Erc-Mg values (2.42 +/- 0.41 (after) versus 2.17 +/- 0.4 mmol/l (before), 11/17) and this supplementation improved PDD symptoms in 23/33 children (p < 0.0001) with no adverse effects: social interactions (23/33), communication (24/33), stereotyped restricted behavior (18/33), and abnormal/delayed functioning (17/33); 15/33 children were improved in the first three groups of symptoms. When the Mg-B6 treatment was stopped, PDD symtoms reappeared in few weeks. A statistically significant relationship was found in Erc-Mg values from children before treatment and their mothers. In conclusion, this study suggests that the behavioral improvement observed with the combination vitamin B6-magnesium in PDD/autism is associated with concomitant modifications of Erc-Mg values.

Assessment of social functioning in depression.

Impairment of social functioning is a significant aspect of depression distinct from the symptoms of depression. Social functioning defines an individual's interactions with their environment and the ability to fulfill their role within such environments as work, social activities, and relationships with partners and family. The analysis of social functioning has arisen from a growing interest in measuring the consequences of depression and antidepressant therapy. Impairment often persists long after the resolution of symptoms by pharmacotherapy, and is not extensively assessed by the traditional scales to measure the intensity of depressive symptoms. Assessment is influenced by the method used, and there is an increased awareness that the patient's perspective should be foremost. Several scales for the evaluation of social functioning have already been developed, ranging from those requiring a structured interview with a trained assessor to self-assessment scales. In constructing such tools, a balance must be found between the amount of detail required to produce a clear account of the patient's social functioning and the ease of use in large multicenter studies. The newest scale is the Social Adaptation Self-evaluation Scale (SASS), specifically for self-assessment of social functioning by patients with depression. It contains 21 items covering the different aspects of social interactions, global social attitude, and self-perception. The SASS has been validated and found to be simple to use and sensitive to changes in the different areas of social functioning. Recently, the SASS was used to demonstrate the greater efficacy of reboxetine, a new selective noradrenaline reuptake inhibitor (selective NRI), compared with the selective serotonin reuptake inhibitor (SSRI) fluoxetine, in improving social functioning in patients with depression. Specifically, the SASS was able to show that reboxetine improved patient motivation and self-perception. The SASS is another tool for the evaluation of the extent and quality of the response to treatment and may also help to elucidate the roles of noradrenaline and serotonin in depressive illness.

Androstenedione and progesterone production in vitro by the inner or the outer theca cells in preovulatory follicles of gonadotropin stimulated calves.

This study reports some of the steroidogenic characteristics of the interna and externa theca cells taken from young and eCG primed calves. These cells were isolated from large healthy follicles. The were separately cultured for 3 days in absence or in presence of steroid substrates. Androstenedione (A4) and progesterone (P4) were measured by radioimmunoassay (RIA). In control conditions, A4 levels, higher in interna than in externa cells (P < 0.001), decreased during cultures (P < 0.01). In both cell types, A4 increased in presence of 17 alpha-hydroxypregnenolone (17OHP5), pregnenolone (P5) and 22R-hydroxycholesterol (22R-chol)(*P < 0.05) but not with P4 or 17 alpha-hydroxyprogesterone (17OHP4)(P > 0.05). The most efficient substrate was dehydroepiandrosterone (DHEA) (P < 0.005). In control conditions, P4 levels increased in both cell types. They were higher in externa than in interna cells on day 1, the reverse was observed on day 3. P4 levels increased after addition of 22 R-chol and P5 (P < 0.005) but not with 17OHP5, 17OHP4 and DHEA (P > 0.05) from day 1 in externa cells and only on day 3 in internal cells. P4 levels measured on day 1 were lower than the quantity of P4 added as a substrate. These results, obtained with theca cells from young calf follicles, indicate: 1/A4 is synthesized by the delta5 pathway and 17 alpha-hydroxylase activity decreases in vitro, 2/externa and interna cells differ by the quantities of A4 and P4 produced, 3/both lack precursors to produce A4 and P4 but their 3 beta-hydroxysteroid dehydrogenase activity subsists, 4/P4 could be metabolized during the first 2 days in both cell cultures.

Steroid productions by co-cultures of granulosa cells with inner and outer theca cells in preovulatory follicles of gonadotropin stimulated calves.

Granulosa, interna and externa theca cells were isolated from large follicles of equine-chorionic-gonadotropin (eCG)-primed calves and co-cultured during 3 days in the absence or in the presence of dehydroepiandrosterone (DHEA). Co-cultures were performed by adding defined numbers of theca and/or granulosa cells which represented 0, 10, 20, 50 or 100% of total cells per well. Secretion of oestradiol-17beta (E2), androstenedione (A4) and progesterone (P4) depended on the type of theca cells (P < 0.001), on the percentage of seeded granulosa cells (P < 0.001) and on the day of culture (P < 0.001). DHEA increased (P < 0.001) E2 and A4, but not P4 (P > 0.05) productions. Interactions existed between these factors (P < 0.01). On day 1, A4 production was nil in granulosa cells alone. E2 production was negligible in theca cells alone but it increased when granulosa cells were added. E2 and A4 varied in an opposite manner according to the percentage of granulosa cells and with the type of theca cells. On day 3, without DHEA, E2 and A4 were low. On day 3 with DHEA, E2 production was maintained in granulosa cells alone but not with any combination of theca cells. In these conditions, A4 production was maintained in the presence of theca cells but not in granulosa cells alone. Granulosa cells alone secreted more P4 than theca cells. P4 increased as a function of the percentage of granulosa in co-cultures with externa but not interna theca cells with which it remained low. In conclusion, theca cells in culture have two effects in relation to the granulosa cells, which differ according to the steroid concerned and to the cell combination. Both types of theca cells have an inhibitory effect on E2 secretion whereas only interna theca cells are able to alter P4 production.

Do noradrenaline and serotonin differentially affect social motivation and behaviour?

In a placebo-controlled 8-week study comparing the selective noradrenaline re-uptake inhibitor (NARI), reboxetine, with the selective serotonin reuptake inhibitor (SSRI), fluoxetine, in major depression, patient social motivation and behaviour were investigated through a newly developed 21-item self-rating scale, the Social Adaptation Self-evaluation Scale (SASS). At last assessment the mean SASS total score was significantly superior on both reboxetine (n = 103) and fluoxetine (n = 100) compared with on placebo (n = 99). In addition, the SASS total score in the reboxetine group was significantly higher compared with the fluoxetine group. At point-biserial correlation analysis, all but one item discriminated reboxetine from placebo, while only 12 items discriminated fluoxetine from placebo. In the reboxetine-fluoxetine comparison, nine items showed a positive association with reboxetine, while the opposite was never seen; the association was maximal in the area of negative self perception and lack of motivation towards action. These results support, at social functioning level, a differential effect of selective manipulation of the noradrenergic or serotonergic system in keeping with the long-debated hypothesis on the specific involvement of serotonin in regulating mood and of noradrenaline in sustaining drive.

Development and validation of a social functioning scale, the Social Adaptation Self-evaluation Scale.

The Social Adaptation Self-evaluation Scale (SASS) is a 21-item newly developed scale for the evaluation of patient social motivation and behaviour in depression. The scale was submitted to a validation procedure based on the data from a general population survey in 4000 individuals and from two controlled studies comparing the new selective noradrenaline reuptake inhibitor (NARI), reboxetine, with placebo and/or fluoxetine in 549 patients with major depression. The scale was shown to be valid, reliable and sensitive to change. The results of the multivariate analyses allowed the identification of three principal factors and five clusters. In view of its simplicity of use, and of its peculiar characteristic of investigating patient perspective on self and environment perception and on social motivation and behaviour, the scale represents a useful additional tool for the evaluation of social functioning in depression and will facilitate the development of new antidepressants with differential effects in this domain in depressed patients.

Follicular growth and ovarian dynamics in mammals.

General characteristics of female reproductive activity, such as seasonality, cyclicity and triggering of ovulation differ widely among mammals, but common mechanisms underlie ovarian function. In all mammals, follicles begin to grow from a pool of primordial follicles constituted early in life, continuously throughout the life of the female. Follicular development involves two phases. In a first phase (basal follicular growth), follicles grow slowly and follicular growth rate is tightly related to proliferation of granulosa cells. Basal follicular growth is mainly under the control of growth factors of paracrine origin. In these follicles, FSH may exert an indirect mitogenic effect on granulosa cells by enhancing expression of growth factors or growth factor receptors. In a second phase (terminal follicular growth), follicular growth is rapid and occurs by enlargement of the antrum. In addition, it is accompanied by important changes in differentiation of follicular cells. Terminal follicular development is strictly dependent on gonadotrophins. FSH plays determinant roles in enhancing granulosa cell differentiation and survival. These actions are mediated or modulated in an important way by paracrine factors, particularly steroids and growth factors. LH stimulates steroidogenesis in theca cells and sustains terminal maturation of granulosa cells in preovulatory follicles. Follicular growth, atresia and ovulation are accompanied by important tissue remodelling processes, which are under the fine control of proteinases and inhibitors of proteinases. In particular matrix metalloproteinases and their inhibitors are probably involved in the control of rapid terminal follicular growth and regression of atretic follicles as well as in follicular rupture at ovulation.

Noradrenaline-selective versus serotonin-selective antidepressant therapy: differential effects on social functioning.

The outcome of antidepressant therapy in terms of social functioning was evaluated in a randomized, placebo-controlled, double-blind study comparing the selective noradrenaline reuptake inhibitor (NARI), reboxetine, with the selective serotonin reuptake inhibitor (SSRI) fluoxetine. Of the 381 patients with major depression participating in the study, 302 patients were assessed using the new self-rating Social Adaptation Self-evaluation Scale (SASS). Mean SASS total score at last assessment was superior (p < 0.05) to placebo for both reboxetine and fluoxetine. Moreover, reboxetine was superior (p < 0.05) to fluoxetine. Evaluation of the sensitivity to change in individual items by point-biserial correlation analysis showed a significant correlation between improvement in item score and reboxetine treatment in all but one item for the reboxetine-placebo comparison. In the fluoxetine-placebo comparison, a significant correlation was evident for only 12 of the 21 items. Direct comparison of reboxetine with fluoxetine revealed a significant correlation between change in item score and treatment for nine items, in favour of reboxetine. The association was maximal for six items, mainly related to negative self-perception and to active social behaviour. In the subset of patients in remission at last assessment (n = 91), the mean SASS total score for reboxetine was superior to that of both fluoxetine and placebo (p < 0.05). Point-biserial correlation analysis revealed that most items sensitive to change under active treatment in the total population did so with reboxetine (17 items) or fluoxetine (nine items) in patients in remission. In the reboxetine-fluoxetine comparison, 14 items showed a significant association with reboxetine treatment. In conclusion, while social motivation and behaviour in depression are significantly affected by both noradrenergic and serotonergic antidepressant treatment, noradrenergic therapy seems particularly effective in improving negative self-perception and motivation towards action, resulting in a better quality of remission in terms of social functioning.

[Hyperprolactinemic amenorrhea:treatment with cabergoline versus bromocriptine. Results of a national multicenter randomized double-blind study]. / Aménorrhée hyperprolactinémique: traitement par cabergoline versus bromocriptine. Résultats de l'étude nationale, multicentrique, randomisée, en double insu.

OBJECTIVES: Cabergoline is a new, long-acting D2 agonist, highly effective in suppressing prolactin and restoring gonadal function in hyperprolactinaemic amenorrhoea. This study compares its efficacity and safety with that of the reference compound, bromocriptine. METHODS: A prospective study involved 21 French Centres and 120 women, with hyperprolactinaemic amenorrhoea, randomized to either cabergoline (CAB 0.5-1 mg twice weekly) or bromocriptine (BRC 2.5-5 mg twice daily). Treatment is given under double-blind conditions for the first 8 weeks, and subsequently in open conditions in further 16 weeks with dose adjustments according to response. Patients were assessed for biochemical and clinical efficacy and drug safety (adverse symptoms and biology). RESULTS: Normoprolactinaemia was achieved in 56/60 (93.3%) taking CAB and 27/58 (48.2%) taking BRC (p < 0.0001). Ovulatory cycles or pregnancy were recorded in 71.6% and 48.2% of patients (p = 0.001). Prolactin suppression to below 50% of the baseline value was observed in 1.6% and 15.5% (p = 0.007). Adverse symptoms were recorded in 31/60 (51.6%) and 40/58 (69.2%) patients respectively in the double-blind period, and 53.3% versus 65.5% for the full course of the study. There were significantly fewer gastro-intestinal symptoms in the CAB group, 36.6% versus 84.5% (p < 0.0001). CONCLUSION: Cabergoline is a new prolactin-lowering drug, more effective and better tolerated with fewer gastrointestinal symptoms than the reference compound, bromocriptine.

Ontogenesis of somatic and germ cells in sheep fetal testis.

Testicular development of sheep fetuses was studied between day 42 of gestation and birth. Testis mass and the total number of testicular cells increased curvilinearly with fetal age and a positive linear relationship was established between the logarithmic values of age and testis mass, sex cord total length, total number of Sertoli cells, germ cells and Leydig cells per testis. The mean number of gonocytes per unit length of sex cord, the Sertoli cell nuclear cross-sectional area and the Leydig cell cross-sectional area decreased linearly with age between day 42 of gestation and birth. Hypophysectomy and hemicastration were performed to study the regulation of testicular cell divisions during fetal life and to determine whether they were under pituitary control and whether a feedback mechanism was present. Hypophysectomy at day 100 or 110 of gestation nonsignificantly decreased (0.05 < P < 0.01) the testis mass, total length of sex cords and total number of Sertoli cells and significantly decreased (P < 0.05) the cross-sectional area of Leydig cells and nuclei of Sertoli cells. Sex cord diameter and total number of gonocytes were unaltered. Hemicastration at day 110 of gestation significantly increased (P < 0.05) the total number of Leydig cells per testis without changing any other testicular parameter. In male sheep fetuses, the proliferation of testicular somatic and germ cells occurs throughout testicular fetal growth at a higher rate before day 100 of gestation than later, but without any differentiation. Mitotic divisions of Sertoli cells are more numerous before birth than afterwards. Before birth, the proliferation of gonocytes is not under pituitary control.

Lack of pharmacokinetic interaction between the selective dopamine agonist cabergoline and the MAO-B inhibitor selegiline.

The addition of a dopamine agonist and of a monoamine oxidase type B inhibitor to I-dopa has been suggested in the therapy of Parkinson's disease. The plasma pharmacokinetics of both cabergoline and I-dopa have previously been shown to remain unaffected when the two drugs are given concomitantly. This study aimed at examining whether the plasma pharmacokinetic parameters of cabergoline and selegiline are modified when given in combination. Selegiline is hardly detectable in plasma. Therefore, the plasma levels of its metabolites amphetamine, methamphetamine and desmetylselegiline were used to assess the effect of cabergoline co-administration. Plasma levels of the selegiline metabolites were determined first after selegiline administration (10 mg/day) for 8 days, and then after administration of both drugs for 22 additional days (day 30). Cabergoline plasma levels were measured on day 30, and then after administration of cabergoline (1 mg/day) alone for further 22 days. No statistical difference was found between the Cmax.ss, tmax.ss, AUC0-24h.ss, C0h.ss, C24h.ss values of cabergoline and of the selegiline metabolites when the two drugs were given alone or in combination, indicating the absence of pharmacokinetic interaction between cabergoline and selegiline.

[Changes in the utero-placental and fetal cerebral circulations induced by nicotine in the ovine fetus]. / Modifications des circulations utéro-placentaire et cérébrale foetales induites par la nicotine chez le foetus ovin.

Foetal and maternal circulations were studied in 5 gestating sheep given an intra-muscular nicotine injection (10 mg) daily for 65 days beginning on the 60th day of gestation. Six control sheep and 5 others given a placebo injection comprised the control group. Placental (Rp), cerebral (Rc) and uterine (Ru) vascular resistances were measured by Doppler at the following sites: umbilical arteries, foetal cerebral arteries, uterine arteries. Measurements were taken at 80, 100 and 130 days of gestation. The Doppler resistance indices were comparable in the control and placebo group. The cerebral Doppler resistance indices were comparable in the three groups at 80 and 100 days, but there was a significant increase at day 130 in the nicotine group (p < 0.01). This increase was in favour of reduced cerebral perfusion. The umbilical indices were slightly higher at 80 and 130 days in the nicotine group (p < 0.01). The cerebro-placental ratio (Rc/Rp) remained unchanged in the controls, but increased significantly in the nicotine fetuses (p < 0.05) confirming a redistribution of the fetal blood flow away from the brain. There was no significant difference in the uterine resistances at 80 and 100 days in the nicotine group (p < 0.01), but they increase between 100 and 130 days. In the control and placebo groups, delivery occurred at normal gestation dates. In these two groups, two lambs (10%) were stillborn. In the nicotine group, premature delivery occurred in two sheep and 8 of the 13 lambs (63%) were stillborn.(ABSTRACT TRUNCATED AT 250 WORDS)

Nicotine-induced changes in the cerebral circulation in ovine fetuses.

Pulsed Doppler ultrasound was used to investigate fetal and maternal ovine circulation in 16 ewes. Resistance index (R) was measured at the following sites: umbilical, fetal cerebral, and uterine arteries. Measurements were performed at days 80, 100, and 130 of gestation, day 0 being the day of mating. Normal ranges of the Doppler indices were delimited on the six control ewes. Five ewes were treated by intramuscular injection of 10 mg of nicotine 5 days per week and five others received placebo injections. No difference was found on the Doppler indices between the control group and the placebo group. The cerebral indices did not differ in the three groups at days 80 and 100 but were significantly higher at day 130 in the nicotine group in comparison to the two others (p less than 0.01). The umbilical indices were slightly elevated at days 80 and 130 in the nicotine group. No significant difference was found on the uterine indices at any of the three stages of gestation whatever the treatment. In the control and placebo groups the ewes delivered in the normal ranges of gestation length. In these groups 2 of 20 lambs (10%) died at birth. In the nicotine group 2 ewes delivered prematurely and 8 of the 13 lambs (62%) were stillborn. In conclusion, repeated nicotine injections induce vasoconstriction on the umbilical and cerebral arteries of the fetus at the end of the gestation and are associated with poor perinatal outcome.

[Use of the Adinfer diagnostic system in a study of somatic disorders in general practice]. / Emploi du système d'aide au diagnostic Adinfer dans une étude sur la plainte somatique en médecine générale.

Somatic complaints are very common in general medical practice. They are not identified as psychic disorders and are treated symptomatically. We explore two kind of problems: 1. methodological problems such as the instruments to use to examine somatic complaints (it is evident that a checklist does not give the best results with suggestible patients); and 2. the relationships between somatic complaints and psychic disorders such as anxiety, depression and somatoform disorders. Psychiatric nosology is by no means clear and includes many diagnoses from "hysteria" to "hypochondria" or "psychosomatic", "somatization". In this study, we compare the symptoms collected by general practitioners, and their clinical diagnoses to those obtained by an automatic DSM-III diagnostic program. Adinfer was modified so that three DSM decision trees were systematically scanned: depressive, anxiety and somatoform disorders. This allows for an epidemiological study of somatic complaints and their relationship to depression and anxiety. The subjects' score on rating scales for anxiety and depression are compared with the diagnoses made by the expert system. We discuss the significance of somatic symptoms, the DSM classes and the value of expert systems in epidemiological studies.

Photoperiodic regulation of the time of birth in rats: involvement of circadian endogenous mechanisms.

A resonance experiment was undertaken to demonstrate that photoperiod regulates birth time by endogenous circadian mechanisms. Pregnant rats were maintained on a standard light-dark (LD) cycle (14L-10D; lights on from 0600 to 2000 hr) or on fixed LD cycles with periods of 12, 24, 36 and 48 hours after day 8 of gestation. In these groups, the light phase (2 hr) started between 0600 and 0800 hr or between 1800 and 2000 hr illuminating exclusively (for periods of 24 and 48 hr) or alternatively (for periods of 12 and 36 hr) the hours corresponding to morning (M) or evening (E) of the standard light regimen. At the end of gestation, the general activity was manifested mainly at moments corresponding to the night of the standard regimen in most groups; it was delayed in the two groups lit up exclusively at E hours. In groups receiving light exclusively at M hours, birth times were delayed compared to the deliveries in groups receiving light at E hours only. An intermediate distribution of birth times was observed when M and E hours were stimulated every 12 hr but not every 36 hr. The apparent stability of the diurnal rhythm of activity and the difference in birth time distributions due to the period of light phase indicate that the regulation of birth time by photoperiod is due to a circadian mechanism in rats. This mechanism implicates at least two endogenous systems which are apparently antagonists with regard to birth.