Severe psychiatric side effects observed during prophylaxis and treatment with mefloquine.

Mefloquine hydrochloride is now one of the major antimalarial drugs used both in prophylactic and therapeutic regimens. Large-scale studies have shown that it is efficacious and relatively well tolerated. However, some severe side effects, particularly neuropsychiatric reactions, have been described. We describe two young men with no previous medical history who experienced severe psychiatric reactions during prophylactic and curative mefloquine therapy. In both cases, full recovery was rapid after cessation of the therapy. There is no explanation for these reactions. Serum levels of mefloquine were within the normal range. The absence of contraindications and minor side effects during an initial course of mefloquine should be confirmed before another course is prescribed.

The cortical serotonin2 receptors studied with positron-emission tomography and [18F]-setoperone during depressive illness and antidepressant treatment with clomipramine.

BACKGROUND: Changes in serotonin (5-HT)2 receptor densities were reported in depression by postmortem studies and following treatment with tricyclic antidepressants in animal studies. Here, 5-HT2 receptors were studied in vivo in depressed patients. METHODS: Cortical 5-HT2 receptors were investigated prospectively using positron-emission tomography and [18F]-setoperone in 7 depressed patients, before and after at least 3 weeks of clomipramine (CMI), 150 mg daily. They were compared to 7 age-matched controls. RESULTS: There was no significant difference between the untreated patients and the controls, except in the frontal region, where the [18F]-setoperone specific binding was slightly lower in patients. After CMI treatment, depression scores significantly improved and [18F]-setoperone specific binding decreased in cortical regions, suggesting receptor occupancy and/or receptor regulation, by CMI; however, no clinical score correlated with the 5-HT2 receptor measurements either in the untreated or in the treated conditions. CONCLUSIONS: These data substantiate the view that tricyclic antidepressants such as clomipramine significantly interact with cortical 5-HT2 serotoninergic receptors in actual therapeutic situations.

Left prefrontal glucose hypometabolism in the depressed state: a confirmation.

The resting-state cerebral metabolic rates for glucose of 10 severely depressed patients (seven bipolar and three unipolar) were compared, before and after treatment with tricyclic antidepressants, to those of 10 control subjects of similar age by means of positron emission tomography and the fluorodeoxyglucose method. Significant left-right prefrontal asymmetry was present in the patients before but not after successful treatment, suggesting that medication can reduce this asymmetry. Also, significant hypofrontality and whole-cortex hypometabolism were found in the patients in the depressed state and persisted in the treated state, despite clinical improvement, suggesting that these abnormalities are not state dependent.

Frontal 5-HT2A receptors studied in depressive patients during chronic treatment by selective serotonin reuptake inhibitors.

To investigate adaptative changes of 5-HT2A receptors induced by SSRIs, six patients chronically treated for a depressive episode (four with fluoxetine, two with fluvoxamine) were studied with PET and [18F]setoperone. They were compared to eight untreated depressive patients. The mean frontal to cerebellum radioactivity concentration ratio, an index of the [18F]setoperone specific binding to 5-HT2A receptors, was higher in treated than in untreated patients, when age was taken into account. This suggests that chronic treatment by SSRIs could induce an up-regulation of the 5-HT2A receptors, and that 5-HT2A receptor down-regulation is not a common mechanism for the therapeutic effects of all serotoninergic antidepressive drugs.

Context-dependent information processing in patients with schizophrenia.

Thirty schizophrenic patients fulfilling the Diagnostic and Statistical Manual of Mental Disorders IV criteria for schizophrenia and 30 control participants were shown a set of incomplete sentences, and were asked to complete them with the first word(s) that came to mind. Target sentences included an ambiguous word, the ambiguity of which was not resolved within the clause. However, completion necessarily required participants to select one specific meaning. Each target sentence was preceded by another sentence playing the role of context, which was designed to prime the less frequent meaning of the ambiguous word. The results showed that schizophrenic patients, especially those with thought disorder [on the basis of their TLC scores (Thought, Language and Communication Scale; Andreasen, N.C., 1979. Thought, language and communication disorders. Clinical assessment, definition of terms and evaluation of their reliability. Diagnostic significance. Arch. Gen. Psychiatry 39, 778-782)], used the most common meaning of the ambiguous word more frequently than controls, thus revealing a specific deficit in context use. The deficit was observed whether or not the relation between context and target sentences was made explicit. These results are in line with the cognitive models of schizophrenia that postulate a decreased ability to use context information. However, when considered in the light of prior studies (e.g., Bazin, N., Perruchet, P., 1996. Implicit and explicit memory in patients with schizophrenia. Schizophr. Res. 22, 241-248), they suggest that the deficit in processing contextual information is limited to what Baddeley (Baddeley, A.D., 1982. Domains of recollection. Psychol. Rev. 98, 708-729) called the interactive context (which affects the meaning, or the interpretation, of the target event) in contrast to the independent context (which does not interfere with the meaning-based interpretation of the target event).

No serotonin 5-HT2A receptor density abnormality in the cortex of schizophrenic patients studied with PET.

To investigate putative abnormalities of cortical 5-HT2A receptor density in schizophrenia, we used positron emission tomography and [18F]setoperone, a high-affinity 5-HT2A receptor radioligand, in 14 neuroleptic-free or -naive schizophrenic patients and in 15 normal controls. No significant difference between the groups was observed in the whole or regional cortical binding potential of [18F]setoperone, indicating an absence of major 5-HT2A receptor cortical density abnormalities in schizophrenics.

Presynaptic dopaminergic function in the striatum of schizophrenic patients.

The dopaminergic hypothesis of schizophrenia postulates increased brain dopaminergic activity. Two previous studies reported increased 18F-DOPA uptake with positron emission tomography in schizophrenic patients (n = 5, n = 7). In the present study, striatal dopaminergic function was assessed in vivo in six untreated schizophrenics and seven control subjects, comparable for age and sex. The 18F-fluoro-L-DOPA (18F-DOPA) uptake rate constant Ki was determined in the caudate and putamen using coregistered positron emission tomography and magnetic resonance imaging. No difference between groups for mean Ki was found. The variability of the 18F-DOPA uptake values was higher in the caudate (p < 0.01) and in the putamen (p < 0.001) in schizophrenic patients than in control subjects, suggesting that schizophrenia is a disorder involving heterogeneous states of the striatal presynaptic dopaminergic function.

Apolipoprotein E gene polymorphism in early and late onset bipolar patients.

To explore the involvement of apolipoprotein E gene (APO E) in major depression, we studied the APO E gene polymorphism in a sample of 156 unrelated bipolar patients and 91 healthy volunteers. This population was stratified for age at onset of the affective disorder (onset before 18 years, after 45 years and between 18 and 45 years). Early onset bipolar patients with psychotic symptoms exhibited a significant increase of epsilon4 allele frequency (28.9%) compared to either other bipolar patients (13.1%, chi2 = 6.52, df = 1, P < 0.02) or controls (12.1%, chi2 = 7.01, df = 1, P < 0.01). The association between epsilon4 and early onset bipolar disorder (BPD) with psychotic symptoms suggests that APO E gene is a risk factor for a subgroup of BPD, or influences the phenotypic expression (i.e. psychotic symptoms or age at onset) of manic depressive illness.

Self-concept and mood: a comparative study between depressed patients with and without borderline personality disorder.

Within the framework of Self-Structure Theory, this study investigated the relationship between depressed mood and Borderline Personality Disorder (BPD) on self and others descriptions, with a special emphasis on the self-structure's valence, that is, its affective, negative and/or positive content. Seventeen DSM-III-R unipolar depressed patients with associated BPD (DSM-III-R axis II) and twelve unipolar depressed patients without BPD were compared to eighteen non-psychiatric controls on four measures of evaluation and of affective discrepancy of descriptions of self and others. Subjects were administered the grid repertory technique. The analysis of the resulting two-way valence matrix, with attributions as columns, and self and others as rows, showed that depressed patients with and without BPD differed from the non-psychiatric controls with regard to negativity of the descriptions. As compared with the two other groups, depressed patients with BPD showed a distinctive pattern characterised by the joint presence of a negative view of self and a larger affective discrepancy for others, with others being conjunctively assigned positive and negative attributes. Despite some limitations, the distinctive pattern evidenced corroborates the conflicted interpersonal relationship and is in keeping with clinical theorising on BPD.

Mood congruence effect in explicit and implicit memory tasks: a comparison between depressed patients, schizophrenic patients and controls.

This study investigates mood congruence effect in explicit and implicit memory tasks in 23 inpatients fulfilling DSM-III-R criteria for major depressive disorder. Performances were compared to those of 15 in- or outpatients fulfilling DSM-III-R criteria for schizophrenia, and 37 normal subjects serving as euthymics controls. All subjects were submitted to a standard cued recall test and to a word stem completion test devised to assess the effect of the initial presentation without the explicit retrieval of the words being necessary. The material used for these two tasks consisted of emotionally negative and positive words. The results show a mood congruence effect in the ;;;implicit;; memory task (and not in the ;;;explicit;; memory task) only in patients who had recovered from their major depressive episode (and not in depressed patients, schizophrenic patients, or controls). These results suggest that implicit and explicit emotional information processing differ from one another in certain respects.

Six-month and lifetime prevalences of psychiatric disorders in inpatients with diabetes mellitus.

The Composite International Diagnostic Interview (CIDI) was used to assess the prevalence of psychiatric disorders in a French population of 46 inpatients with diabetes mellitus. According to DSM-III-R criteria, 52.2% of subjects presented at least one psychiatric diagnosis in their lifetime and 41.3% did so less than six months before the study. Affective and anxiety disorders represented at least 83% of the psychiatric diagnoses. The risk for those disorders seems to be restricted to a predisposed group as only one of the 16 subjects who had suffered from an anxiety or depressive episode within the previous six months had never experienced such an episode before.

[Long-term outcome of alcoholic patients after a stay in a hospital hepatogastroenterology unit]. / Devenir des malades alcooliques après une hospitalisation en hépato-gastroentérologie.

The long term results of psychologically oriented treatment for alcoholism were evaluated in 147 patients hospitalized in a liver unit and followed for 1-5 years. Twenty-three percent of the patients were hospitalized for treatment of alcoholism, while 61 percent were hospitalized for alcohol-related disease. The main patient characteristics were: males: 71 percent; age: 48 +/- 10 years (mean +/- SD); alcoholic cirrhosis: 48 percent; initial request for help in abstinence: 9 percent; and unemployment: 35 percent. During the hospitalization (16 +/- 10 days), each patient had 1 to 4 psychotherapeutic interviews. Seventy-four percent of patients responded to follow-up after discharge and contact was maintained in 23 percent of patients 2 years thereafter. The only two independent prognostic variables for long-term follow up were the need for medical supervision (P less than 0.001) and employment (P less than 0.005) (Cox model). Only 10 percent of the patients attended a post-hospitalisation psychotherapeutic program. Among the 108 patients who were followed, 35 percent were totally abstinent immediately after discharge and 17 percent did not relapse during the 2 following years. Relapse was unpredictable according to any of the initial variables. Half of the patients who were abstinent immediately after discharge remained totally so at long-term follow-up. Total abstinence was obtained for 39 percent of patients during a mean period of 27 +/- 34 months. Medical, social, or psychological improvement was observed more often in abstainers (61 percent) than in non abstainers (11 percent, P less than 0.001). We conclude that: a) long-term follow-up and abstinence were infrequently obtained in unselected alcoholic patients hospitalized in a liver unit; b) no initial criteria could predict the alcoholic relapse or select patients for alcoholism treatment; c) long-term results seemed more favorable when the patients where totally abstinent immediately after discharge.

[Symptomatology of inhibition]. / Sémiologie de l'inhibition.

This essentially descriptive paper deals with inhibition as a symptom or as a behavior pattern and studies the different areas of; inhibition of the intellect (i.e. a decrease in though production witnessed by disorders of language flow), reduced attention span (distractability, inability to concentrate), inhibition of volition (abulia, indecisiveness), memory inhibition (in the sense of selective amnesias, post-crisis amnesias, cyclical amnesias), restriction of the basic drives (which can touch the life principle, the need for sleep, hunger, sexual drive), emotional inhibition including a feeling of inferiority and self-doubt which affects interpersonal relations: in this sense inhibition can also manifest itself in experiences of estrangement and depersonalization. A dynamic study of inhibition should first deal with the presumed relationship between the symptom and a specific pathological process and analysis of the underlying inconscious mecanisms.

[Hyperthymic disorders]. / Les hyperthymies.

Hyperthymia, as referring to the book by J. Delay: "les dérèglements de l'humeur" (1946), means from a clinical point of view, an exaggeration of the level of mood, as well on the one hand, expansive and joyful, as, on the other hand, distressing, within a withdrawn self. K. Schneider had described an hyperthymic personality in 1923: optimist, dynamic, taking initiatives, or more simply hypomanic. He opposed this type of personality to depressive personality types. Delay unified these two pathologic evolutions within a physiopathological and psychopathological unique concept. Conversely, H. Ey denied this unique affective conceptualization of the disease. From his physiopathologic jacksonian point of view, a certain level of destruction of consciousness explains, solely, both affective and noetic disorganization of these so called hyperthymias. Since the early eighties, Angst, Akiskal, Cassano, brought up to date the adjective hyperthymic. They assessed the correlation between premorbid personality disorder and mood disorder: a number of bipolar disorders are linked with premorbid hyperthymic disorders. This was the K. Schneider' position who linked traits and states, as Kraepelin did for the manic premorbid disposition. Choosing a dimensional approach, one question has to be asked: can hyperthymia be found as a previous personality trait of different other diseases? An anxious hyperthymia can be found linked to some panic attacks and other neurotic symptoms. A delusional hyperthymia is described by Janzarik who thinks that delusional ideas are linked to a kind of delusional mood. G. Petit, in 1933, subsumed the existence of a paranoid hyperthymia within the more general concept of the passional psychoses described by de Clérambault, Delmas and Borel.

[Psychosensorial manifestations observed in psychotic patients treated with betamimetic drugs]. / Manifestations psychosensorielles observées chez des psychotiques soumises à des médications bêta-mimétiques.

We report four observations of women who had acute or subacute psychotic crisis and who were stabilized without any manifestation. In order to delay delivery these women received during pre-partum high doses of beta-mimetic drugs (isoxsuprine and salbutamol). Such a prescription seems to have been responsible of acute and transient psychotic symptoms similar to those observed in drug-induced psychosis (derealisation preceeding depersonalization, visual and auditory hallucinations, anxiety). Recently Gluckman has described a similar case to those reported here. But in his case the conditions of coming out were different and there was a lack of psychotic antecedents. Previous works concerning "psychotic-like" effects of beta-blokers rise the question of possible psychodysleptic effects of beta-mimetic drugs.

[Benzodiazepines. Long-term prescription and withdrawal]. / Benzodiazépines. Prescription au long cours et sevrage.

The authors successively mention the long-term treatments with benzodiazepines, prescribed by the general practitioner and by the psychiatrist. In conclusion, they state that the benzodiazepines seldom induce dependence. Then, reviewing the data available in the literature , they describe the clinical features of withdrawal syndrome, the factors with may be prescribe and the rebound phenomena following abrupt cessation of benzodiazepine therapy.

[Drug discontinuation in depression]. / Arrêt du traitement médicamenteux dans la dépression.

Before stopping or starting medications in depression, the first step is a through assessment of the patient's mood disorder: past medical general and psychiatric history, psychological profile, past specific treatment history... Today some data are well demonstrated: antidepressant or lithium or carbamazepine discontinuation should be done gradually (over weeks or months) and with an intensive medical follow-up; after the acute treatment of the index depressive episode, a full therapeutic dose of the antidepressant agent should be continued for at least 4 to 6 months; antipsychotic drugs and minor tranquilizers use should be limited: combination of a neuroleptic and an antidepressant in depression with psychotic features, combination of a minor tranquilizer in depression with anxiety during the first three weeks if necessary. A contario the timing and the method of discontinuing maintenance treatment (lithium or antidepressant) have not been well studied. Literature data are discussed: frequency of recurrence during treatment discontinuation, even after long-term euthymia; possible risk for developing rapid-cycles or non response after lithium discontinuation. More precise clinical guidelines are necessary.

[An open study of Mianserin (author's transl)]. / Etude ouverte de la mainsérine.

The authors present a synthesis of 277 observations collected in France from open studies of mianserin. The product has shown positive results in 65 per cent of the patients considered, based on the global clinical judgement of the prescriber at the beginning and the end of a 28 days open study. The data from Hamilton's scale for depression and Beck's Inventory, even though concerning a smaller number of patients, seem to provide similar results. The improvement appears from the first week, and seems to concern the overall depressive mood, anxiety, psychomotor inhibition, and sleep. The evaluation of the respective results for each target-symptom is made difficult due to the lack of precise data concerning the associated psychotropic drugs. Tolerance has generally been good; there have only been five drop-outs as a result of unpleasant side effects.

[The Pleasure-Displeasure Scale. Use in the evaluation of depressive illness]. / L'échelle de plaisir-déplaisir. Utilisation dans l'évaluation de la maladie dépressive.

The Pleasure-displeasure Scale is a self-report instrument consisting of 82 items for measuring the intensity of subjects' affective responses to usually pleasant and unpleasant situations. 81 depressed inpatients were compared to 120 normal subjects. The responses of the depressed patients to the Pleasure sub-scale (French translation of the Fawcett-Clark's Pleasure Scale) are more anhedonic than those of the normal subjects; but the difference did not reach statistical significance. Pleasure scores in the depressive group are bimodally distributed; a distinct subset (11% of depressives) is characterised by an extremely anhedonic Pleasure score. The sensitivity to unpleasant stimuli is significantly greater in the depressive group; however this difference seems to be related rather to a low cultural level than to depression itself. Finally pleasure and displeasure scores are closely correlated: this could possibly imply that anhedonia is not an independent symptom but rather belongs to the wider constellation of affective anesthesia.

[Negative schizophrenic symptomatology and the P 300 potential]. / Symptomatologie schizophrénique négative et onde P 300.

We studied the latency and amplitude of the P 300 wave of event-related potentials (P 3) in 19 hospitalised schizophrenic patients. We used an odd ball paradigm procedure in acoustic stimulation. We found a negative correlation between the amplitude of P 3 and negative schizophrenic symptomatology, measured by the negative BPRS score and the SANS score. However, no link would appear to exist in our study between positive symptomatology and P 3 amplitude. The correlation with the negative BPRS score is found in both evaluations, at the beginning and at the end of the period of hospitalisation. P 3 latency would appear to be independent of either positive or negative schizophrenic symptomatology. It would thus appear to us that the negative symptomatology, rather than the positive, could be at the origin of marked changes in P 3, observable fro relatively simple experimental but parameters such as reaction time or error scores remain to be specified, even if they appear to intervene infrequently. The use of event-related potentials would thus appear pertinent in clinical research and could help in the homogenisation of schizophrenic populations studied.