Optimal duration of risperidone or olanzapine adjunctive therapy to mood stabilizer following remission of a manic episode: A CANMAT randomized double-blind trial.

Atypical antipsychotic adjunctive therapy to lithium or valproate is effective in treating acute mania. Although continuation of atypical antipsychotic adjunctive therapy after mania remission reduces relapse of mood episodes, the optimal duration is unknown. As many atypical antipsychotics cause weight gain and metabolic syndrome, they should not be continued unless the benefits outweigh the risks. This 52-week double-blind placebo-controlled trial recruited patients with bipolar I disorder (n=159) who recently remitted from a manic episode during treatment with risperidone or olanzapine adjunctive therapy to lithium or valproate. Patients were randomized to one of three conditions: discontinuation of risperidone or olanzapine and substitution with placebo at (i) entry ('0-weeks' group) or (ii) at 24 weeks after entry ('24-weeks' group) or (iii) continuation of risperidone or olanzapine for the full duration of the study ('52-weeks' group). The primary outcome measure was time to relapse of any mood episode. Compared with the 0-weeks group, the time to any mood episode was significantly longer in the 24-weeks group (hazard ratio (HR) 0.53; 95% confidence interval (CI): 0.33, 0.86) and nearly so in the 52-weeks group (HR: 0.63; 95% CI: 0.39, 1.02). The relapse rate was similar in the 52-weeks group compared with the 24-weeks group (HR: 1.18; 95% CI: 0.71, 1.99); however, sub-group analysis showed discordant results between the two antipsychotics (HR: 0.48, 95% CI: 0.17; 1.32 olanzapine patients; HR: 1.85, 95% CI: 1.00, 3.41 risperidone patients). Average weight gain was 3.2 kg in the 52-weeks group compared with a weight loss of 0.2 kg in the 0-weeks and 0.1 kg in the 24-weeks groups. These findings suggest that risperidone or olanzapine adjunctive therapy for 24 weeks is beneficial but continuation of risperidone beyond this period does not reduce the risk of relapse. Whether continuation of olanzapine beyond this period reduces relapse risk remains unclear but the potential benefit needs to be weighed against an increased risk of weight gain.

Crystallization and preliminary diffraction studies of two quinoprotein alcohol dehydrogenases (ADHs): a soluble monomeric ADH from Pseudomonas putida HK5 (ADH-IIB) and a heterotrimeric membrane-bound ADH from Gluconobacter suboxydans (ADH-GS).

Crystals of a soluble monomeric quinocytochrome alcohol dehydrogenase (ADH-IIB) and of a trimeric membrane-associated quinocytochrome alcohol dehydrogenase (ADH-GS) have been obtained. The ADH-IIB crystals are triclinic, with one monomer in the unit cell, and were obtained in the presence of PEG 8000, sodium citrate, HEPES buffer and 2-propanol. X-ray data were collected at 110 K to 1. 9 A resolution (R(merge) = 6.4%) and the orientation of a methanol dehydrogenase search molecule (from Methylophilus methylotrophus W3A1) was obtained by molecular replacement. Preliminary refinement of this model (10.0-3.0 A resolution, R = 0.37, R(free) = 0.40) led to tentative identification of the two highest peaks in a native anomalous difference Fourier map as the Fe atom of the heme and a calcium ion interacting with the PQQ prosthetic group. The ADH-GS crystals are tetragonal, displaying six similar lattices, both primitive and centered, and were grown by the sitting-drop method after replacement of Triton X-100 by dodecylmaltoside or octaethylene glycol monododecyl ether in the presence of ammonium sulfate and sodium acetate buffer, with and without PEG 3500 and calcium ion. The best diffraction is obtained at 110 K where the resolution extends to about 4 A in the a and b directions and about 3 A in the c direction.

Clinical psychomotor retardation and attention in depression.

The importance of the cognitive component in depressive clinical psychomotor retardation is well-recognized, but the underlying information-processing dysfunction has not been precisely investigated. Thirty unmedicated major depressives were concurrently assessed using the Depressive Retardation Rating Scale (DRRS) and an attentional battery in order to evaluate selective and divided attention. Results were analysed following dimensional and categorical approaches. The depressive episode intensity and the associated anxiety did not correlate with any of the attentional variables. However, significant correlations were observed between the DRRS score and every attentional task. Results of the categorical analysis contrasting attentional performances of depressives with and without clinical psychomotor retardation argued for the existence of a link between psychomotor retardation and a global attentional deficit. This study attests to the value of clinical psychomotor retardation as a predictor of cognitive deficits in depressed patients.

Distractibility and processing resource deficit in major depression. Evidence for two deficient attentional processing models.

Performance on the Stroop Color-Word Test is impaired in depression, but it is not clear whether this impairment reflects a distractor inhibition disturbance or a reduction of processing resources. In this study, untreated major depressives were evaluated using a modified computerized Stroop Test composed of three tasks: to name the color of XXXXXs, of nonconflicting words, and of conflicting color words. It was hypothesized that, unlike color words, nonconflicting word distractors would disturb the color naming task only in the presence of a primary distractor inhibition disturbance. The slow reaction time (RT) depressives and normal RT depressives, according to their color naming speed without distractors, were contrasted to distinguish depressives with and without clear signs of resource deficit. It was found that interference produced by nonconflicting words was greater in normal RT depressives than in either slow RT depressives or control subjects, while interference caused by color words was dramatically stronger in slow RT depressives than in other groups. Results suggest the existence of two different attentional deficit patterns in clinical depression: some depressives have a distractor inhibition disturbance while others are deficient in processing resources.

Are there differential effects of fluoxetine in retarded/blunted affect versus agitated/anxious depressives? A clinical study.

BACKGROUND: Clinical selectivity of antidepressants with pharmacological specificity still remains under debate. METHOD: In the open trial presented below, the effects of fluoxetine, a selective serotonin re-uptake inhibitor (SSRI), were compared across two groups of depressive inpatients contrasted on their symptomatological expression (agitated/anxious versus retarded/blunted affect). Sixteen patients (8 in each groups) were included in the 4-weeks treatment period and submitted to a weekly-based evaluation. Global depression, retardation, emotional blunting, agitation, anxiety and mood profile were assessed. RESULTS: Significant improvements of the HDRS and MADRS scores were observed in both groups. Although no group x treatment interaction was found on the global scores of depression, a differential effect according to the group was observed on anxiety, agitation, irritability and emotional lability. DISCUSSION: These preliminary results support the hypothesis that the effect of fluoxetine on positive clinical dimensions could lead to a differential effect in patients with agitation/anxiety when compared with patients with retardation/blunted affect.

Attention disturbance in clinical depression. Deficient distractor inhibition or processing resource deficit?

Cognitive impairments in depression have recently been proposed as secondary to more basic attentional disturbances. Studies have shown that performance on the Stroop Color-Word Test is impaired in depressives, but it is not clear whether this impairment reflects a primary distractor inhibition disturbance or a more global cognitive dysfunction, such as a reduction of processing resources. In the present study, unmedicated clinical depressives were evaluated using a computerized Stroop Color-Word Test and the Visuo-Spatial Interference Test, a selective attention task that makes fewer demands on resources. Compared with normal subjects, depressives presented increased choice reaction times (CRT) and interference in both tests. Correlations were found between CRT and interferences only in depressives, favoring the processing resource hypothesis. Further exploratory analysis comparing the more rapid depressives and the slower normal subjects on CRT revealed that although these subgroups had comparable CRT, rapid depressives still exhibited increased interference on the Visuo-Spatial Interference Test. Thus, in non- or mildly retarded patients, a specific distractor inhibition deficit was observed in absence of resource deficit.

Neuroleptic associated tardive dyskinesias in young people with psychoses.

BACKGROUND: Apart from ageing, the factors associated with vulnerability to the emergence of tardive dyskinesia are poorly defined. METHOD: Risk factors associated with the presence of a chronic choreic or dystonic disorder were assessed in a cross-sectional comparison of anamnestic and clinical data in a homogeneous group of 64 young psychotic patients (under 40 years of age) on chronic low to moderate doses of neuroleptics. RESULTS: Dyskinetic subjects presented more indirect indicators of occult brain damage, such as a perinatal event or traumatic brain injuries in infancy and early childhood; neurological examination showed more anomalies in dyskinetic patients than in nondyskinetics, with a higher prevalence of facial release reflexes. CONCLUSION: These data may support the hypothesis that occult acquired brain damage is important in the genesis of this 'drug-induced' disorder.

SSRIs in anxious-agitated depression: a post-hoc analysis of 279 patients.

A post-hoc analysis of nine controlled antidepressant trials examined the intensity of the initial anxiety and agitation of depressed patients improved by SSRIs compared with depressed patients improved by norepinephrine (NE) reuptake inhibitors, mixed NE/serotonin reuptake inhibitors and placebo. We report that SSRI responders were more anxious-agitated than NE reuptake inhibitor responders, suggesting a preferential efficacy of SSRIs in agitated depression.

[Involvement of the basal ganglia in obsessive compulsive disorder: a review]. / Implication des noyaux gris centraux dans le trouble obsessionnel-compulsif: une revue.

This article reviews the main clinical indicators linking the basal nuclei to obsessive compulsive disorder (OCD). Various pathologies associated with lesions of the basal nuclei are examined, followed by a review of neuropharmacological, brain imaging and psychosurgical studies. Once the role of the neostriatum in ritualistic behaviours has been clarified, the symptoms of OCD are interpreted based on the hypothesis of a lesion of the striato-orbito-frontal loop.

Organic brain dysfunction and cognitive deficits in young schizophrenic patients with tardive dyskinesia.

Tardive dyskinesia (TD) has been associated with cognitive deficits, especially in older psychiatric patients on neuroleptic medication. This study investigated the relationship between presence of TD, organic brain dysfunction (OBD), and cognitive deficits in young psychiatric outpatients maintained on minimal doses of oral neuroleptics, with anticholinergics prescribed only on as-needed basis. Sixty-four patients, aged 20-39 years, were evaluated for the presence of abnormal movements, localizing and nonlocalizing physical signs, and deficits in memory, ability to shift, and sustained attention. Sixteen patients showed definite signs of TD. Significant associations were found between TD and OBD, and between cognitive deficits and OBD, but not between TD and cognitive deficits. Significant regression predictors of TD were the interaction between OBD and previous dystonia, as well as duration of neuroleptic treatment. These findings suggest that some potential risk factors for TD already identified in the literature also apply to younger patients with relatively shorter exposure to neuroleptics. However, the results indicate that the relationship between movement disorders and cognitive deficits may be more apparent in older patients.

Early onset of lithium-associated hypothyroidism.

In general practice, psychiatrists are confronted with the difficulty of structuring a rational design for the early detection of hypothyroidism. To determine the period during which a patient receiving lithium is most at risk of developing hypothyroidism, a retrospective study was conducted on the records of 154 patients at two general hospital lithium clinics from January 1980 to August 1991. Forty-two cases of hypothyroidism (clinical hypothyroidism and/or abnormally elevated levels of TSH) were detected. A significant difference was found between the onset of hypothyroidism and age (older patients developed more thyroid dysfunction), but no significant differences were found between thyroid abnormality and sex or diagnostic category and menopausal status, although trends were observed for the two former variables. This longitudinal study is the first to describe an outline of thyroid functioning in terms of the duration of treatment. Lithium-associated hypothyroidism develops most often during the first two years. Of the 42 cases of hypothyroidism, 16 were diagnosed within six months (38%), 23 within the first year (55%), and 31 two years (74%). Since thyroid functioning is an important parameter in the course of affective disorders, its close and frequent monitoring is mandatory during the first two years of treatment.

[Dysmorphophobia (body dysmorphic disorder)]. / La dysmorphophobie (trouble dysmorphique physique).

This article reviews the historical and terminological origins of dysmorphophobia from Herodotus to today. It explains the differences pointed out by many authors, including the DSM-III-R, between body dismorphic disorder and delusional disorder somatic type, which are referred to as monosymptomatic hypochondriacal psychoses in Europe. Epidemiological data, clinical characteristics and outcome are discussed. Explicative theories and neurobiological, developmental and analytical aspects of body image are presented. The association between body dismorphic disorder and other disorders is analyzed, and treatment possibilities are discussed. The authors suggest that body dismorphic disorder be classified with obsessive compulsive disorder, whatever the intensity of symptomatology, rather than with somatoform or delusional disorder, and treated with serotonin uptake inhibitors or neureptics that have been proven to be effective for the treatment of this disorder, such as pimozide.

The dimensional approach to clinical psychopharmacology: a polysemous concept.

The last decade has seen significant progress in the development and specific clinical application of selective psychotropes. The dimensional approach to clinical psychopharmacology views the behavioral targets of psychotropes as phenomena existing on a continuum and as components, in varying degrees, of most psychopathologies. The modern concept of dimension has been used in different contexts. In psychology it has a mathematical sense, whereas in biological psychiatry it is associated more with biological function. This paper reviews these two concepts and the recent models attempting to merge them into one. The heuristic value of the dimensional approach, as well as some of its pitfalls and new avenues of research, are discussed.

[Pathological gambling: literature revue]. / Le jeu pathologique: une revue de la littérature.

This paper summarizes the current literature on pathological gambling. Interest in gambling has been present in every society but treated as an object of sociopolitical or literary interest. It is only from the beginning of this century that psychiatry began to look at pathological gambling, first with Freud and his writing on Dostoïevsky then with other theories like the learning theory, studies on substance dependence, the links with affective syndromes and the psychobiological studies. These studies are presented and discussed. Finally, the authors offer some guidelines for an approach to a pathological gambler.

Corpus callosum agenesis and psychosis in Andermann syndrome.

Recent illustrations by cerebral magnetic resonance imaging of anomalies of the corpus callosum in schizophrenics have kindled renewed interest in this association. We studied 62 patients affected by the Andermann syndrome, a polymalformative familial syndrome combining frequent congenital corpus callosum agenesis, mental retardation, psychotic episodes, peripheral neuropathy, and some dysmorphic features. Twenty of 62 patients presenting with psychosis were compared with 20 nonpsychotic patients matched according to sex and age. The psychotic patients presented an atypical psychosis as defined by the Diagnostic and Statistical Manual of Mental Disorders, Third Edition, beginning in postadolescence. No significant relationship was observed between corpus callosum agenesis and psychosis. However, a significant association between posterior fossa atrophy and psychosis was established in our study. Although there are limitations in using cross-sectional data for this purpose, the findings suggest an association between cerebellar anomalies and schizophrenialike syndrome and rule out an implication of developmental callosal defects in such psychiatric disorders.

[Perphenazine enanthate. Results of a 1-year open multicenter study]. / Enanthate de perphénazine. Résultats d'une étude ouverte multicentrique d'un an.

The results of a one-year, open multicenter trial of perphenazine enanthate, a sustained-release neuroleptic drug, are reported. 240 patients (62% suffering from schizophrenia) were included in the study and 144 were followed during the 12-month period. The usual adverse reactions associated with sustained-release neuroleptic drugs were observed. Total and partial BPRS ratings showed that improvement (expressed as a percentage) after 12 months' treatment was similar for systematized chronic delusions, paranoid schizophrenia and hebephrenia. However, the onset of therapeutic activity was different in these three groups of patients. Maximum therapeutic activity, as defined by the BPRS rating, was obtained within 4 months in chronic delusions whereas schizophrenia improved more progressively. Such patients therefore require prolonged treatment before the therapeutic activity of a sustained-release neuroleptic drug can be assessed.

[Essential arterial hypertension and quality of life. Comparative crossed double-blind study of labetalol and captopril]. / Hypertension artérielle essentielle et qualité de vie. Essai comparatif en double-insu croisé du labétatol et du captopril.

The purpose of this multicenter randomised, double-blind and cross-over study was to compare the antihypertensive effects of labetalol (L) and captopril (C) in 42 moderate hypertensive patients (mean age: 52 years). The drugs were given during two 4-weeks periods at the end of which the systolic (SBP) and diastolic blood pressures (DBP) were measured at rest in supine and standing positions. The assessment of the quality of life was realized with 4 scales completed by the practitioner [anxiety, depression, well-being, visual analog scale (VAS)] and 4 scales of auto-assessment completed by the patient [2 VAS, well-being, sub-scale of pleasure]. At the end of the first treatment's period (D28), both drugs had decreased significantly supine SBP and DBP (p less than 0.001), standing DBP (L = p less than 0.01; C = p less than 0.05), while only L lowered supine SBP (p less than 0.01). The cross-over analysis was unable to conclude, due to the number of patients and a significant interaction which reduced its power. Thus the effect of the first treatment's period seemed to influence the efficacy of the second one. The percentages of patients with a controlled BP were respectively: after 4 weeks of treatment, L = 61 p. 100 vs C = 42 p. 100 and at the end of study (D56), L = 67 p. 100 vs C = 64 p. 100.(ABSTRACT TRUNCATED AT 250 WORDS)