Cognitive impairment in long-term high-dose diazepam abusers (dose > 30 mg diazepam/day; duration of abuse > 12 months) was examined by administering four memory-related tests and comparing the outcomes with those of matched controls. Deficits were found in spatial and visual learning, spatial and visual short-term memory (STM) as well as for spatial and visual long-term memory (LTM). As for verbal aspects of memory, solely the acquisition of novel verbal material (verbal learning) was impaired, Furthermore, deficits in a concentration task were observed. In chronic abuse the established memory deficits are similar to cognitive impairment after single doses. Relaxing or anxiety-reducing effects of diazepam were no longer present. The results of this experimental study demonstrate the risks of diazepam use beyond therapeutic range.

We present the values for the amount of transitions, for the total stage duration and for the first time of occurrence (latency) of a stage. A test aimed at evaluating probability values for the transition from one sleep stage to another was applied to the hypnograms of ten patients with endogenous depression and of ten normal controls. Sleep data (EEG, EMG, EOG) of each subject were recorded on magnetic tape and paper for three consecutive nights. Following sleep stage classification, portions of hypnograms of 480 min, further divided into sub-periods, were retained for the purpose of the test. The results proved that significant differences between depressed and control subjects exist among the data corresponding to various sleep stages. These findings also provided useful statistical indications in order to reduce the amount of computing needed by an automatic classifier.

Les données neurochimiques directes ou indirectes obtenues dans différentes affections du système nerveux central (SNC) constituent la base rationnelle de I'utilisation des médicaments dans des indications précises. Les antidépresseurs (AD) tricycliques agissant sur les principales amines du SNC trouvent ainsi des applications thérapeutiques variées en dehors de la dépression. L'arrivée de nouveaux AD au mécanisme d'action, soit plus cibé (la sérotonine), soit différent (IMAO) pose de nouveau cette question des indications psychiatriques et neurologiques, qui ne peut être résolue que par des essais méthodologiquement irréprochables. Une telle approche évitera d'ignorer pendant des années des effets thérapeutiques incontestables d'une molécule ancienne, tel que ce fut le cas de la clomipramine dans les troubles obsessifs-compulsifs.

The main symptoms of Gilles de la Tourette syndrome (GTS) are motor and vocal tics, but there are also several psychiatric disturbances such as obsessive compulsive symptoms (OCD) and mutilations. The etiology and pathophysiology of this basal ganglia disorder are unknown. Though many patients benefit from therapy with dopamine antagonists, the effect is often insufficient. Therapeutic efficacy of the opiate antagonist naltrexone has been described in recent years. Ten patients (three f, seven m) with GTS were invesitgated in a seven-week, open dose-response trial, using naltrexone in doses ranging from 12.5 mg to 200 mg/day. The severity of the GTS symptoms were rated with the Yale Global Tic Severity Scale (YGTSS) and the Tourette Syndrome Global Scale (TSGS); OCD was estimated by the Maudsley Obsessive Compulsive Inventory (MOCI). The course of tics and psychopathology was assessed by three self-report scales, and two scales rated by clinicians (Clinical Global Impression, CGI; Brief Psychiatric Rating Scale, BPRS). Only two patients showed improvement of the GTS. In four patients, no effect was observed, whereas the other four patients exhibited deterioration. One patient finished the complete trial, three patients dropped out because of lack of improvement, and four because of deterioration of the symptoms. Considering the mean values, no improvement of GTS could therefore be observed, and because of the unpredictable effect, the study was stopped after ten patients. Nevertheless, the effects were quite controversial. The opiate system seems to be affected only in some of the GTS patients in a clinically relevant manner, and opiate antogonists can either improve or provoke GTS symptoms. Pathophysiologically different subgroups of GTS may contribute to the controversal results.

Meta-analysis of several double-blind, placebo-controlled studies, including 1277 patients, has been performed in order to compare the efficacy of moclobemide, a new reversible and selective MAO-A inhibitor (RIMA) and imipramine. The main interest of the analysis was to test the time course of improvement and the impact of the pre-defined outcome criteria (50% reduction of total HAMD score) on the response to treatment, if initial severity of depression and drop-outs due to inefficacy are taken into consideration. In order to analyze the interdependence of the severity of the disease and outcome, patient sample was subdivided into three HAMD (17 items) baseline score groups: low- (score ≤ 21), medium- (22-27) and high (≥ 28) scorers. We found that reliable assessment of the point in time at which a drug begins to show therapeutic effect in each individual is a critical factor in the determination of the time course of improvement. We defined therefore the onset of improvement as the time point of a significant decrease (20%) of HAMD baseline score without subsequent deterioration. The threshold for the distinction between a significant change and spontaneous fluctuations, or error variations due to instrument or observer, was the natural variability of the HAMD score during the first two observation days. The results of the analysis replicated our earlier findings and confirmed that in treatment responders the time course of improvement is identical under placebo and antidepressants. Neither the time-points of the onset of effect, nor the time-points at which a 50% decrease of HAMD was reached, differed between the groups. In particular, no treatment- Specific time lag showed up in the onset of action. The difference in efficacy between antidepressants and placebo was evident only in the total number of responders and non-responders. Moreover, onset of improvement within the first 10 days of treatment, which was observed in 40-50% of patients, was highly predictive of the final response to treatment. The rate of correctly predicted responders in our sample was 70% for all three treatment modalities. With respect to the severity of the disease, a slight shift towards earlier onset of improvement was found for more severe cases. This finding was true for placebo and drug responders hut there was no clear-cut other interdependence with the treatment outcome. Drop-out rales due to inefficacy were in this study similar under all treatments (20-24%) anil occurred mostly during the first two weeks of the trial (64-71%.).

We describe a simple method to objectively identify the threshold for edge detection in morphometric measurement of brain structures. This method correlates highly with the subjective operator-driven approach to edge detection. While the objective approach, using a histogram of pixel intensities, reduces rater bias and may reliably identify brain-CSF boundaries, its value in morphometric measurements of smaller cerebral structures may be somewhat limited.

Patterns of interaction and attitudes in the relationships of 21 young schizophrenic patients, their parents and therapists were explored and compared with each other in this pilot study. The focus was on expressed emotion (EE), which was revealed to have an important impact on the course of the illness. In this study, the EE status of the relatives as well as of the therapists was rated using the five-minute speech sample method. Furthermore, data on the quality of interaction of therapists and parents with the patients were derived from the therapist/relative-patient interaction scale. Results showed that one-third of both the therapists and the parents were rated high on EE. High-EE relatives were rejected and perceived as inscrutable by the patients. The assessment of the therapeutic and familial relationships demonstrated the patients’ need for unequivocal communication. Differences and similarities in the interaction styles, and their implications for research and therapy are discussed.

A study was conducted on a group of 73 patients suffering from major depressive disorder (DSMIII) compared with 120 normal subjects using a subscale of physical pleasure (Fawcett Clark pleasure capacity scale-physical pleasure, FCPCS-PP). The major depressives were significantly more anhedonic than the normals and the distribution of the FCPCS-PP scores in these subjects was unimodal.

Vitamin B12 deficiency can result in a variety of neurological and psychiatric disorders. We describe a young patient in whom vitamin B12 deficiency presented as dementia with only mild hematological disease and no spinal cord disease.

Calcium channel blockers increase the capacity of the urinary bladder. The antienuretic activity of verapamil was examined in young adult enuretics. Eleven drug-free, healthy, sleep-related enuretic males, were treated for two weeks with verapamil (240 mg, per os, at 9 pm). Verapamil failed to display an antienuretic effect.

Family rituals consisting of ceremonial acts, traditions and patterned interactions serve as a basis of communication, collective identity, and stabilizing relationships. Therefore, the measurement of rituals in a schizophrenic family is an objectification of the family's symbolic communication and integration. Based upon this, the relationship between family rituals practice in 138 families both with a schizophrenic member (71) and without (67) was examined by the use of an originally developed instrument, the “Family Rituals Scale” (FRS). The psychometric properties of this instrument were tested and proved to be reliable. Families with a schizophrenic member were less ritualizing than the “normal” families. The correlation between FRS scores and Global Assessment Scale scores in schizophrenic patients was negative (the higher the psychosocial functioning level, the lower FRS scores), which means a higher performance of family rituals. The effect of other factors on FRS scores and the therapeutic implications are discussed.

Four pregnancies in three panic disorder patients are described. In three pregnancies panic symptoms improved initially, but worsened in the second half. One patient developed panic disorder in the second half of her pregnancy. Changes in balance between progesterone and estrogen could explain this clinical course.

Today it appears that a general consensus exists concerning the methodological principles to be used in establishing the efficacy profile of a new drug in anxiety disorders, ie a double-blind, parallel group design testing different doses of the new drug versus placebo (Angst et al, 1993; Rickels, 1990), however there is also growing concern about increasingly high placebo response rates and important differences between countries in these trials. This seems to be true despite the fact that in recent years, selection criteria for diagnosis and severity of the disorders have become more clearly defined and more restrictive than in the past.

This situation increases the risk of false negative results in otherwise well designed clinical trials with new anxiolytic drugs and can incite pharmaceutical companies to abandon the further development of efficacious compounds even if they have potential advantages in terms of safety over the available products.

Keller and Shapiro (1982) reported that 26% of the first 101 patients who entered the National Institute of Mental Health (NIMH)-Clinical Research Branch Collaborative Program on the Psychobiology of Depression (Katz and Klerman, 1979; Katz et al, 1979) with a major depressive episode were found to have a pre-existing chronic minor depression of at least 2 years’ duration. They labeled this Phenomenon “double depression„ (Keller and Shapiro, 1982). Furthermore, patients with panic disorder almost universally suffer from major depression at some time in the course of their disorder (Coryell et al, 1988; Stein and Uhde, 1988; Vollrath et al, 1990). “Double diagnosis„, or identification of psychotic or related syndromes, co-existing with personality disorders, have received much attention in the literature in recent years (Sanderson et al, 1990; Torgersen, 1990; Barsky et al, 1992). Much of the research on comorbidity between depressive and anxiety disorders has been summarized in two edited volumes (Kendall and Watson, 1989; Maser and Cloninger, 1990).

L'oblet de cette brève revue de la littérature est d'indiquer les principaux axes de recherche et de reflexion sur la complémentarité des approches psychodynamiques et psychologiques.