[Assessment of mental states at risk of psychotic transition: validation of the French version of the CAARMS]. / Évaluation des états mentaux à risque de transition psychotique: validation de la version française de la CAARMS.

This article aims to present the validation study of the French version of the Comprehensive Assessment of at risk mental states (CAARMS), an interview that seeks to determine whether young adults criteria for at-risk (AR) mental states, or psychosis. We assessed 40 young subjects, 15 were considered as "prodromal" (Prd) and 10 as experiencing a first episode of psychosis (PEP) by our expert clinician at the center - centre d'évaluation des jeunes adultes et adolescents, University Hospital Centre, Paris - and 15 were healthy controls matched for age and sex. When assessed with the CAARMS, 73 % (n=11) of the prodromal subjects reached the criteria for AR mental state, four subjects did not reach the criteria for AR, nor psychosis (P) and 100 % of the PEP reached the criteria for P. The three groups were significantly different on CAARMS total score (P<0.001) and subscores ; Prd subjects had intermediate scores between PEP (P<0.001) and controls (P<0.001) scores, PEP showing the highest scores. Post-hoc analysis showed that Prd significantly differed from Controls on each subscale (P<0.001) and that Prd differed from PEP on the "positive symptoms" subscale (P<0.001), as well as on "behavioural change" (P=0.021), owing to difference on the item "impaired role function". We used the brief psychiatric rating scale 24 items with anchor (BPRS24-EA) in addition to with the CAARMS, the AR group showed intermediate scores between controls and P subjects. Total scores of both scales were correlated (r=0.408 ; P=0.043) and the BPRS24-EA "positive symptoms" score was correlated with CAARMS' scores on the "Positive symptoms" subscale (r=0.456, P=0.022), "emotional disturbance" (r=0.506, P=0.01), and "behavioural change" (r=0.666 P=0.001). We found no correlation between BPRS negative and depression subscales and any of the CAARMS' subscales. When looking at its reliability, reliability coefficients (Cronbach's alpha) showed excellent reliability for "positive symptoms", "emotional disturbance", "behavioural change" and "general psychopathology" (respectively r=0.82, 0.75, 0.78, 0.84, 0.83) and moderate reliability for "cognitive change", "negative symptoms" and "motor/physical change" (respectively r=0.39, 0.59, 0.43). Overall, analysis of the results of construct validity, concurrent validity and reliability of the CAARMS indicates that the French version is valid and reliable. It is now available to develop and implement early detection programs in French speaking countries.

[Validation of the French version of the expanded Brief Psychiatric Rating Scale with anchor BPRS-E(A)]. / Validation de la version française de l'échelle abrégée d'appréciation psychiatrique étendue avec ancrage, BPRS-E(A).

INTRODUCTION: The Brief Psychiatric Rating Scale was initially developed as a rapid method to assess symptom change in psychiatric inpatients of various diagnoses. The original version was expanded to an 18-item version and thereafter to a 24-item version to increase sensitivity to a broader range of psychotic and affective symptoms. The latest version of the expanded 24- item BPRS provides probe questions and detailed anchor points for the ratings for each item. LITERATURE FINDINGS: Studies have shown the expanded and anchored 24-item BPRS to be a sensitive and effective measure of psychiatric symptoms with good interrater reliability that can be maintained over time. To our knowledge, there are eight published papers including factor analyses of the BPRS-E(A). While many similarities are evident between these studies, inconsistencies are apparent that may have been due to sample size, characteristics and / or methodological differences in the factor analysis computation. Among these studies, six provided a four-factor solution. There was no French version of this scale available. METHODS: After its translation into French and back translation, we investigated the validity of the French BPRS-E(A) version. We carried out a component analysis on the data of 111 participants of various diagnoses, mostly hospitalised for a first psychotic episode, yielding to a three-factor solution (positive symptoms--disorganisation; depression-anxiety and negative symptoms). RESULTS: A good internal consistency and interrater reliability were found. These results confirm the psychometric value of the BPRS-E(A) in its French version. We compared those findings to earlier reports; similarities and differences are discussed.

[Homicide and major mental disorder: what are the social, clinical, and forensic differences between murderers with a major mental disorder and murderers without any mental disorder?]. / Homicide et maladie mentale grave: quelles sont les différences sociodémographiques, cliniques et criminologiques entre des meurtriers malades mentaux graves et ceux indemnes de troubles psychiatriques?

OBJECTIVES: To establish the social, clinical, and forensic differences between murderers suffering from a major mental disorder and murderers without any psychiatric disorder and, in particular, to compare their respective records of psychiatric symptoms and their respective relationship with their victims. METHOD: We studied 210 forensic examinations of murderers, the offences related to the murders, and the social and clinical information collected from psychiatric court reports on persons convicted of homicide. Firstly, we identified the socio-demographic, clinical and criminological profiles of 210 murderers from which were distinguished murderers with major mental disorder. Then, we compared the profiles of murderers suffering from a major mental disorder with those of murderers without any mental disease. In other words, we compared 37 persons affected with major mental disorder (schizophrenia, paranoiac delusional disorder, and affective disorder) with 73 persons without any mental disorder. We deliberately excluded subjects with personality disorder or abuse of/dependency on drugs, mental retardation or dementia. RESULTS: With the exception of certain variables, murderers with major mental disorder have the same characteristics as others murderers: young man, living alone, with psychiatric and offence records and substance abuse. Murderers with major mental disorder are older (37.8 versus 31.7 years old) than perpretators without any mental disorder, and the former have a psychiatric record more often than the latter (81 versus 32.9%). In addition, contrary to the latter, the former show clinical symptoms of a psychopathological process. Depression, delusional and suicidal ideas are frequent among murderers with a major mental disorder, whereas the persons without mental disorder quarrel or have a row with their victim just before their crime. The victim was known to the perpetrator significantly more often in the major mental disorder group than in the no mental disorder group (94,6 versus 76,7%, p=0,008). The most major mental disorders' homicide was more likely to be against intimates than strangers. The application of the former article 64 or the present article 122-1 of the French Criminal Code are envisaged more often in the major mental disorder group than in the no mental disorder group. CONCLUSION: The main difference between murderers with a major mental disorder and murderers without any mental disorder is the psychopathology of the morbid process which underlies the homicide. Impairment of judgment at the time of the crime should be taken into account. As a clinician, we should focus our attention on general risk factors of violence and homicide (male, young, underprivileged class, abuse of alcohol) and on more specific factors (mental disorder co-morbidities...). To these factors should be added the dynamic characteristics of the meeting of the protagonists.

Preattentional processes and disorganization in schizophrenia: Influence of a 6-week risperidone treatment.

INTRODUCTION: Visual orientation and attention are impaired in schizophrenia. Engagement and disengagement of attention and the ability to prompt responses to a stimulus in patients before and after six weeks of risperidone were compared to controls. METHODS: Ten unmedicated (nine naïve) schizophrenic patients, and eleven controls performed 1) A visual orienting task, the Cued Target Detection task (CTD), with the detection of a visual stimulus in valid, invalid, no cue and double cue trials, two conditions for fixation offset for a modulation of visual fixation: Gap: 200 ms before target; No Gap: simultaneous with target, 2) Choice Reaction Time (CRT 0.5 and 2 s delays). RESULTS: At baseline, patients showed longer RT than controls in CRT, but not in CTD, with in CTD, no facilitation of RT with the gap procedure. The alertness index was almost null in CTD-Gap and comparable to controls in CTD-No Gap. Efficiency to detect attended stimuli (CTD-No Gap) and warning effect (CRT 0.5 s) were negatively correlated to disorganization. After treatment, readiness to act in CRT had decreased. In CTD-No Gap, change in PANSS disorganization was correlated to an increased validity index, change in negative sub-score was correlated to decreased attention cost. CONCLUSION: Untreated patients displayed a deficit of Gap effect and a slowing in sustained attention. Disorganization interfered with warning and visual detection. After treatment, its improvement and negative symptoms improvement were associated with better visual detection. These alterations in visual orienting provide new evidence for an oculomotor dysregulation of attentional engagement in schizophrenia.

[Neurological soft signs in schizophrenic patients and their nonaffected siblings]. / Signes neurologiques mineurs chez les patients schizophrènes et leurs apparentés non malades.

BACKGROUND: Neurological soft signs (NSS) are subtle neurological signs indicating non specific cerebral dysfunction. Several studies have found an excess of NSS in schizophrenic patients compared to healthy subjects. Although NSS have been consistently reported in schizophrenic patients, their clinical relevance and their relation to functional impairment and severity of this disease are not well-clarified. In addition, the presence of NSS in schizophrenic patient's relatives suggests that they could be associated with the genetic liability. OBJECTIVES: To determine the prevalence and scores of NSS in schizophrenic patients and their nonaffected siblings and to examine the clinical correlates of NSS in the schizophrenic patients. METHOD: Sixty-six schizophrenic patients (50 males and 16 females, mean age=31.16+/-7.17 years), were compared to 31 of their nonaffected siblings (22 males and nine females, mean age=32.19+/-5.88 years) and to 60 controls subjects (40 males and 20 females, mean age=30.70+/-6.54 years) without family psychiatric history. NSS were assessed with Krebs et al.'s neurological soft signs scale. It is a comprehensive and standardized scale consisting of 23 items comporting five factors: motor coordination, motor integration, sensory integration, quality of lateralization and involuntary movements or posture. The Simpson and Angus scale for extrapyramidal symptoms was also rated. Clinical assessment of the schizophrenic patients was conducted using the positive and negative syndrome scale (PANSS), clinical global impressions (CGI) and global functioning evaluation (GAF). Psychiatric disorders were ruled out among siblings of schizophrenic patients and control subjects by psychiatric review evaluation, according to the DSM-IV check list. RESULTS: When the total NSS score of 11.5 was considered the cut-off point, the prevalence of NSS was 96.9% in the schizophrenic patients versus 35.5% in the nonaffected siblings (p<0.0001). Schizophrenic patients had also significantly higher NSS total score and subscores than the siblings and control groups. The NSS total score was 19.51+/-5.28 in the schizophrenic patients, 10.77+/-3.38 in their nonaffected siblings and 4.23+/-2.07 in control subjects (p<0.0001). The NSS total score and subscores in the siblings group were intermediate between those of the schizophrenic patients and those of the control subjects. The motor coordination, motor integration and sensory integration subscores were higher in schizophrenic patients and their nonaffected siblings. The NSS total score correlated positively with the negative (p<0.0001) and disorganization symptoms (p=0.001) subscores and total score of PANSS (p=0.004). The PANSS total score and negative and disorganization subscores also correlated positively with the motor integration and quality of laterality subscores of NSS. The NSS total score was significantly correlated with severity of illness (p<0.0001), lower educational level (p=0.002) and poor global functioning (p=0.003). CONCLUSIONS: The association between NSS with negative and disorganization dimensions of schizophrenia supports that neurological dysfunction is an intrinsic characteristic of the illness and may distinguish a subgroup of patients with poor illness course and outcome. The NSS could be a trait marker useful in phenotypic characterization of schizophrenic patients and identification of vulnerability in genetically high-risk subjects.

Memory-guided saccade abnormalities in schizophrenic patients and their healthy, full biological siblings.

BACKGROUND: Ocular-motor inhibition errors and saccadic hypometria occur at elevated rates in biological relatives of schizophrenic patients. The memory-guided saccade (MS) paradigm requires a subject to inhibit reflexive saccades (RSs) and to programme a delayed saccade towards a remembered target. METHOD: MS, RS, and central fixation (CF) tasks were administered to 16 patients who met the criteria for DSM-IV schizophrenia, 19 of their psychiatrically healthy siblings, and 18 controls. RESULTS: Patients and siblings showed elevated MS error rates reflecting a failure to inhibit RSs to a visible target, as required by the task. In contrast to controls, prior errors did not improve MS accuracy in patients and siblings. CONCLUSIONS: The specific characteristics of the elevated MS error rate help to clarify the nature of the disinhibition impairment found in schizophrenics and their healthy siblings. Failure to inhibit premature saccades and to improve the accuracy of subsequent volitional saccades implicates a deficit in spatial working-memory integration, mental representation and/or motor learning processes in schizophrenia.

(AAT)n repeat in the cannabinoid receptor gene (CNR1): association with cocaine addiction in an African-Caribbean population.

Owing to their agonist action on dopaminergic systems, cannabinoids may play a major role in substance dependency and schizophrenia. We examined the (AAT)n triplet repeat polymorphism nearby the CNR1 gene, which encodes human cannabinoid (CB1) receptor, in a male Afro-Caribbean population. The allelic and genotypic distributions were significantly different in non-schizophrenic cocaine dependents (n = 97), schizophrenic cocaine dependents (n = 45) and matched controls (n = 88) (P < 10(-4)). The frequency of the (AAT)12 repeat allele was increased in non-schizophrenic cocaine dependents and schizophrenic cocaine dependents vs controls (25.3 and 26.7 vs 5.7%) (P < 10(-4)). Our results support that the (AAT)n polymorphism nearby the CNR1 gene could be associated with predisposition to cocaine dependency.

[Short-term effects of a cognitive-behavioural group therapy in social phobia: evaluation of sixty patients]. / Evaluation des effets à court terme d'une thérapie cognitivo-comportementale de groupe dans la phobie sociale: résultats auprès de soixante patients.

This study analyses the short term effects of a cognitive-behavioral group therapy with 60 patients suffering from social phobia according to the diagnostic criteria of the DSM IV. The therapeutic program is based on 12 sessions of 2 hours (for 6 to 9 subjects) and includes exposure, cognitive restructuring and social skills training. The sample included 34 women and 26 men, with an average age of 34.8 years (SD=9.3). Most patients presented generalized social phobia (n=42; not generalized social phobia: n=18), and 24 received at least one comorbid axis I diagnosis. Subjects were evaluated before and after the therapy with instruments measuring the intensity of social phobia (Liebowitz Social Anxiety Scale), the assertiveness (Rathus Assertiveness Schedule), the disability associated with the disorder (Sheehan Disability Scale), anxiety and depression (Hospital Anxiety Depression Scale and Beck shortened Depression Inventory), and self-esteem (Rosenberg Self-Esteem Scale). The results show significant differences (p<0.001) between the pre and the post-test for all instruments. The effect sizes (ES) range from 1.29 (Liebowitz Scale, total score) to 0.51 (Sheehan item 3), exhibiting patients' improvement on all variables. The highest effect sizes are observed with the instruments specifically designed for the assessment of social phobia (Liebowitz, Rathus and Sheehan scales). Our patients show the major improvements in the Liebowitz Scale (ES=1.29), the best indicator for social phobia, concerning the intensity of anxiety in social situations (ES=1.28) and concerning the frequency of avoidance (ES=1.16). Logically, the effect sizes are somehow lower on Sheehan (ES=1.06) and Rathus (ES=1.00) scales, which are less specifically centered on the score symptoms of social phobia. The improvement is also significant but less remarkable in the other measurements. The Hospital Anxiety Depression Scale reveals a reduction in the level of anxiety and depression, however more significant for anxiety (ES=0.88) than for depression (ES=0.60), that is consistent with the fact that social phobia is an anxious disorder. The shortened Beck Depression Inventory confirms the level of depression decreases after therapy (ES=0.67) and we also observe a significant enhancement of self-esteem (ES=0.85). These findings confirm the short-term strong effectiveness of this therapeutic program. The present study shows that the therapeutic cognitive-behavior group techniques used are specifically effective both on the principal symptoms of social phobia as on other psychological aspects, which were not specifically the focus of this therapy, like general anxiety, depression, and self-esteem. However, this efficient study on 60 subjects needs to be extended to the evaluation of long term effects. It also needs to be reproduced to assess personality disorders that may make the treatment more difficult and are frequently comorbid with generalized social phobia.

Effects of lithium on saccadic eye movements in healthy subjects in a ten-day double-blind placebo-controlled cross-over pilot study.

INTRODUCTION: Although previous studies have shown that lithium modifies eye movements or psychomotor speed, no studies have ever explored the predictive saccades or memory guided saccades during lithium administration. We took the objective to determine the influence of lithium in pseudo-random, predictive or memory-guided saccades in healthy subjects with a view to detect reduced psychomotor speed, inability to anticipate incoming events, or working memory deficits. METHODS: A ten day lithium-placebo randomized double-blind cross-over pilot study was carried out with 12 healthy male volunteers. The cognitive assessment included pseudo-random, predictive and memory guided saccades before and after lithium and placebo periods. A biological assay substantiated the lithium effect on TSH and thyroid hormones. RESULTS: There was no change in pseudo-random or memory guided saccades when comparing lithium or placebo administration. However the ratio of anticipated saccades decreased under the lithium sequence while it remained stable under placebo. Also, subjects having lithium serum levels of > 0.5 meq/l had longer latencies in anticipated saccades. CONCLUSION: The findings do not support a major effect of lithium on alertness or on working memory, although the dosage and duration of lithium was sufficient to modify TSH blood level. Nevertheless, lithium treatment was associated with decreased anticipation in predictive saccades, suggesting this could reflect a reduced ability to anticipate quick motor movements and could be related to the well-known effect of lithium as an anti-impulsive medication.

[Visuospatial context processing in untreated schizophrenic patients and relation to disorganization syndrome]. / Traitement du contexte visuospatial chez des patients schizophrènes non traités -- influence de la désorganisation.

AIM: Previous studies on schizophrenia have suggested that context-processing disturbances were one of the core cognitive deficits present in schizophrenia. Schizophrenic patients have a failure either of inhibition strategy and maintenance of visuospatial information (25) in condition of contextual interference. In the present study, we explored the performances of untreated schizophrenic patients with 2 tasks exploring detection and long term retention of complex visual features and field dependence-independence tasks were selected. These abilities involve temporary maintenance of visuospatial information and executive functioning of visual working memory system. Several studies have shown that cognitive deficit may depend on schizophrenic symptomatology. However results remain controversial in determining the specific influence of negative and positive symptomatologies as well as clinical disorganization. Our goal was to explore the processing of spatial context and its relation to disorganized syndrome. This study was approved by the local ethic committee. METHODOLOGY: Thirty-six schizophrenic patients were included according to DSM IV criteria (19 neuroleptic naïve, 17 unmedicated patients during more than 3 months). Thirty-six healthy controls were matched to patients for age, gender and level of education. Absence of axis 1 pathology was attested for controls with SCID-NP. Current symptomatology was evaluated by the Positive and Negative Syndrome Scale (PANSS) (14). Clinical disorganisation was evaluated with the disorganisation score established upon a factorial analysis of PANSS by Lepine and Lançon. Items selected to distinguish the disorganised group were abstraction, disorganization, orientation, and attention. PROCEDURE: Two tasks of embedded figures were administered individually to patients and controls. The Faverge task (Research of Figures-RF) (10) evaluates the ability to recognize the target from spatial complex geometrical figures. The Group Embedded Figure Task (GEFT - Oltman) assesses the detection and maintenance of visual target and its recognition within a complex figure. Performance between patients and controls were compared with the Student T test. The comparison of two clinical subgroups of disorganized and low disorganized patients and control group was performed with an ANOVA. Tuckey test was used for pairwise comparisons. RESULTS: We defined two subgroups of patients, disorganized patients (subscore 12, n=17) and low disorganized patients (subscore<12, n=19). Theses 2 subgroups were similar for age and level of education. Concerning the two tasks, there was no significant difference between schizophrenic patients and normal controls. The comparison between subgroups of disorganized and low disorganized patients, for RF task, showed a decrease of correct answers with disorganized patients (p<0.05). For GEFT task, disorganized patients had a decrease of correct answers p<0.01) and more errors (p<0.01) and omissions (p<0.05). The low disorganized patients exhibited for the two tests comparable performance to controls. The disorganized patients had a decrease of right answers (p<0.05) and more errors (p<0.05) than controls for GEFT task and no significant difference for RF. However, with IQ (evaluated with an abstract reasoning test) introduced as covariate, only correct answers for GEFT task remain significant (p<0.05). DISCUSSION: The weak performance of disorganized schizophrenic patients for two tasks RF and GEFT showed that treatment of visuospatial information was impaired in the first perceptive phase of selection and in the organization of information (RF), especially with the maintenance of visual information in memory (GEFT). By contrast, low disorganized patients demonstrated a correct analytic treatment of elementary processing and visuospatial working memory. CONCLUSION: The severity of disorganization influences the visuospatial context processing and visuospatial working memory. These results show the heterogeneity of cognitive functioning regarding to schizophrenic symptomatologies. This difficulty could be related to a problem of central executive functioning in the visuospatial component of working memory, possibly mediated by the dysfunction of dorsolateral prefrontal cortex.

[Personality tests and gender identification in male transsexuals]. / Tests de personnalité et identification sexuée chez des transsexuels masculins.

The aim of this research project was to study gender identification in male transsexuals compared to male and female controls, using the Rorschach test and the MMPI. In the international literature, many researches have shown that the nature of the human response on Rorschach card III is linked to gender identification, as is the MMPI Mf scale. Ten untreated male homosexual transsexuals and 18 treated and operated male homosexual transsexuals were compared to 10 male and 12 female controls regarding verbal IQ, human content on Rorschach card III and the MMPI Mf scale. Absence of hormonal treatment for the first group of transsexuals was checked by a blood test at the time of the psychological testing. Responses on Rorschach card III were scored according to different kinds of human contents: male (M), female (F), gender-unidentified/neutral (N), bisexual (B), feminine then masculine or the opposite (M/F), and nonhuman (NH). N, B, M/F and NH responses were rare in all Rorschach protocols. As expected, responses given by participants in the control group were significantly more consistent with their anatomical sex than with the opposite sex. Untreated transsexuals do not differ from treated and operated transsexuals on Rorschach data, and both transsexual groups give significantly more female human representations than male controls. Transsexuals' results are similar to female controls. Untreated transsexuals' mean score on the MMPI Mf scale is significantly higher than that of treated and operated transsexuals' score, in the male profile (biological sex). Both groups of transsexuals score higher on the Mf scale in the male profile than in the female profile. The mean Mf score in the male profile is significantly higher than that of male controls, whereas, in the female profile, the mean Mf score is similar to that of female controls. This study shows that for both groups of transsexuals, results are homogenous in respect of Rorschach and MMPI, showing hyper-conformism to self-perceived gender. Results in both groups are similar to results of female controls, but tend to show even more feminine gender identification. The absence of any significant difference between untreated and treated and operated transsexuals seems surprising, suggesting that the hormonal treatment has not had a major impact on gender identification processes. It would doubtless be interesting to study gender identification using even more kinds of data: all human contents in the Rorschach protocol (not just the responses given to card III), MMPI Mf scale, Draw-A-Person Test and Animal-and-Opposite Drawing Test. This would enhance result liability and could provide useful information about how gendter identification processes evolve after surgical sex reassigment.

Phenomenological and comorbid features associated in obsessive-compulsive disorder: influence of age of onset.

BACKGROUND: To explore clinical features of symptoms and comorbidity according to the age of onset of patients suffering from obsessive-compulsive disorder (OCD). METHODS: The survey involved collecting data from both patient members of an OCD association, and a sample of 175 OCD patients seen in OCD specialty practice. All the patients (n=617) responded to a questionnaire on family and personal psychiatric OCD history, phenomenological features of OCD and comorbidity. They were classified according to OCD age at onset [group early age of onset (EO): under 15, group late age of onset (LO): older than 15]. RESULTS: A higher percentage of patients from Group LO complained of OCD triggering by factors such as professional difficulties and childbirth (P<0.05); also they more often had (P=0.05) a sudden onset of symptoms. On the other hand, clinical features, such as superstition and magic thoughts, parasite obsessions and repeating, counting, hoarding, tapping/rubbing and collecting compulsions were significantly more frequent (P<0.05) in EO; likewise, history of tics was more frequent in this group. The existence of comorbid depression (at least one episode) did not show any significant difference between groups. However, depression preceding OCD was more frequent in LO. There was no significant difference in treatment response according to age of onset OCD. CONCLUSIONS: The results showed a clear association of EO with obsessions of superstition and parasites, repetitive compulsions and motor and vocal tics, whereas a sudden onset, triggering factors and a more frequent depression preceding OCD characterized LO.

Double-blind comparative study of the action of repeated administration of milnacipran versus placebo on cognitive functions in healthy volunteers.

OBJECTIVE: The principal objective was to compare the effects of milnacipran, an antidepressant characterized by a dual-action on serotonin and noradrenaline reuptake, with placebo on memory, attention and psychomotor performance in healthy volunteers. The secondary objective was to evaluate the effects of milnacipran on mood, anxiety and vigilance in these subjects. METHODS: In a double-blind crossover randomized trial, milnacipran (50 mg b.d.) or placebo was administered during two periods of 7 days separated by a washout period of 7 days. Memory tests (recall of words, images and coloured bars), tests to evaluate attention and vigilance (squares test, critical flicker fusion test and choice reaction time test) and visual analogue scales for affect and sleep were used. RESULTS: There were no significant differences between milnacipran and placebo groups with respect to the psychomotor functions tested. No differences were observed in the Norris scales for vigilance, anxiety or satisfaction or in the sleep questionnaire (sleep latency, sleep quality and waking). CONCLUSION: Milnacipran, administered at 100 mg per day for 7 days to healthy volunteers, had no effects on cognitive functions.

[Comparison of two assessment tools of antidepressant side-effects: UKU scale versus spontaneous notification]. / Comparaison de deux outils de mesure des effets indésirables d'un traitement antidépresseur: la notification spontanée et l'échelle UKU.

BACKGROUND AND AIM OF THE STUDY: Overall, the efficacy of the newer antidepressants: serotonin selective reuptake inhibitors (SSRI), selective serotonin/norepinephrine reuptake inhibitor (SNRI), noradrenergic and specific serotonergic antidepressant (NaSSA) and tianeptine is similar to that of the tricyclics, and so their acceptability/safety becomes a selection criterion for the clinician. However, side-effect assessment comes up against several difficulties: distinguishing between somatic symptoms caused by the depression and those caused by the treatment -- which assessment tool to use (spontaneous notification, standardized scales that are not specific for the side effects caused by psychotropic drugs, standardised scales specific for the side effects caused by psychotropic drugs, meta-analysis, etc.) -- which data sources to consult (anecdotal reports, reviews, prospective studies), and which data set to use, etc. As a result, the question of the exhaustiveness and reliability of the data consulted by the clinician can arise. We therefore conducted a comparative study in patients treated with these newer antidepressants, of 2 antidepressants side-effect assessment tools: spontaneous notification (SN) versus the UKU scale, a standardised scale specific for the side effects of psychotropic drugs. METHODOLOGY: The depressed outpatients were selected from a psychiatric unit in a French psychiatric hospital and from a non-hospital consulting room. The main inclusion criteria were: male or female subjects, suffering from major depression without melancholia or psychotic features or suffering from mood disorders (according to DSM IV criteria), who had been treated for at least 4 weeks with one of the newer antidepressants. The main exclusion criteria were: any other psychiatric disorder, a serious physical disorder, treatment with neuroleptics, mood-changing drugs or other antidepressants, and patients who were not able to understand the questionnaire. The investigation was carried out by a clinical pharmacist. RESULTS: Fifty patients were included in the study. There were 18 men and 32 women. The mean age was 53.5 15.9 years [22 - 77], the mean period of treatment was 24 30.5 months [1 - 127] and 52% of the patients received concomitant medication with anxiolitic or hypnotic drug(s). The percentage of patients who reported at least one side effect was significantly higher for the UKU scale than for SN (84% vs 58%, p<0.01). The ratio between SN and UKU scale scores was 2/3. A similar pattern was found for the total number of side effects (n=177 vs n=47, p<0.001). The ratio between the total number of side effects for the SN and UKU scale was 1/4. The side effects were divided into five subgroups: psychiatric, neurovegetative, sexual, neurological and others. In all these subgroups, the number of side effects reported was significantly higher when the UKU scale was used than when SN was used. The values were as follows: psychiatric (n=44 vs n=15, p<0.001), neurovegetative (n=59 vs n=15, p<0.001), sexual (n=36 vs n=10, p<0.001), neurological (n=11 vs n=2, p<0.001) and other side effects (n=27 vs n=5, p<0.001). Nineteen side effects were only reported when SN was used (for example: dry eyes, incompatibility with alcohol, euphoria...). Twenty-four side effects were only reported when the UKU scale was used (for example: increased libido, loss of bodyweight...). The side effects had no impact on daily life in most of 80% of the patients; there was no significant difference between the patient's assessment of the discomfort caused by side effects and the clinician's assessment. In 90% of cases, the side effects did not lead to any change in the treatment. DISCUSSION: The findings of this study show that the collection of data regarding side effects depends on the assessment tool used: the number of side effects reported was significantly higher when the UKU scale was used than when SN was used. However, this finding must viewed with caution, because it has been showed that checklists can induce symptoms in suggestible patients. Neurovegetative troubles are the most commonly reported side effects, and neurological troubles the least often reported. This matches the tolerability profile of these antidepressants. The disorders that were least frequently spontaneously reported were the neurological, sexual and "other" side effects. These emerged only when the clinician asked the patient about them. The 19 side effects that were only reported when SN was used were side effects that were not included in the UKU scale or that had not been present during the three days before we started the investigation. The 34 side effects that were only reported when the UKU scale was used were either side effects with no apparent link with the treatment (for example: micturition troubles) or embarrassing effects (such as increased libido). CONCLUSION: Our findings show that the collection of data on side effects depends on the assessment tool used. These findings need to be confirmed by large-scale comparative studies, and the standardization of the assessment of side effects is a question that needs to be raised.

[Cannabis and schizophrenia: demographic and clinical correlates]. / Cannabis et schizophrénie: données cliniques et socio-démographiques.

UNLABELLED: The high prevalence of psychoactive substance abuse or dependence among schizophrenic patients has now been well established. Mueser et al. stressed the need to assess the abuse of specific classes of substances and analyse the data accordingly. The objective of this study was to compare the socio-demographic correlates and the clinical features in a group of schizophrenic patients with a lifetime cannabis abuse or dependence according to the DSM III-R with a group of schizophrenic patients who had never presented any abuse or dependence. SUBJECTS AND METHODS: The study included 124 subjects with diagnoses of schizophrenia or schizoaffective disorders according to the DSM III-R. Inclusion criteria for participation in the study were age 18 years or older and willingness to provide consent to participate in the study. The inpatients were evaluated when their condition was stabilised. Assessment tools were the psychoactive substance use disorder section of the Composite International Diagnostic Interview (CIDI), the Positive and Negative Syndrome Scale (PANSS), the Global Assessment of Functioning Scale (GAF). Subjects with cannabis abuse or dependence during their lifetime were compared with subjects without abuse or dependence, using chi(2) test for categorical variables and analyses of covariance (ANCOVA) for quantitative variables. RESULTS: Forty-nine subjects (42,6%) presented lifetime abuse or dependence on one or more substances. Since 19 patients with alcohol, stimulant, sedative or opiate abuse or dependence were excluded, the study finally included 96 subjects including a first group of schizophrenic patients with cannabis abuse (n=6) or dependence (n=24) and a second group without any psychoactive substance abuse (n=66). Thirteen (11.3%) patients presented cannabis abuse or dependence within the 6 months prior to the assessment. The mean SD age of onset of cannabis abuse or dependence was 19.6 +/- 3.0 years. Cannabis abuse/dependence preceded the first psychiatric treatment in 70% of the subjects (n=21). 83.3% of the schizophrenic patients with cannabis abuse or dependence were male (n=25) compared to 62.1% in the group without substance abuse (n=41) (chi(2)=4.32, df=1, p=0.04). Schizophrenic patients with cannabis abuse were significantly younger (mean age: 28.9 +/- 6.3 vs 37.0 +/- 12.7, ANCOVA, F=7.2, df=1,96 p=0.009). There was no significant difference between the two groups for marital status, (chi(2)=5.34, df=2, p=0.07), level of education, (chi(2)=0.93, df=2, p=0.62) professional status, (chi(2)=8.7, df=5, p=0.11), on PANSS total score (ANCOVA, F=0.42, df=1,93, p=0.52), GAF score (ANCOVA, F=0.06, df=1,92, p=0.80), mean number of hospitalizations (ANCOVA, F=3.25, df=1,85, p=0.08), mean age of first psychiatric contact (ANCOVA, F=0.74, df=1,93, p=0.39), and neuroleptic dosages (ANCOVA, F=0.03, df=1,90, p=0.87). In contrast, the total duration of hospitalization was significantly longer for the group with cannabis abuse. Patients with cannabis abuse were more likely to have an history of suicide attempts than subjects without substance abuse (chi(2)=11.52, df=1, p=0.0007). DISCUSSION: The prevalence rates for substance abuse and the socio-demographic characteristics of the population of our study are consistent with findings of previous studies. Male gender and age were significantly related to history of cannabis abuse or dependence. Cannabis abuse frequently preceded the onset of psychiatric treatment. However, both schizophrenia and substance abuse tend to develop gradually, with no clear demarcation for the onset of schizophrenia. The absence of any link between the scores for the subscales of the PANSS and cannabis abuse, both in our study and in some retrospective previous studies, is not suggestive of cannabis abuse as a self-medication of positive or negative symptoms of schizophrenia. Self-medication could concern other symptoms, such as cognitive deficits. In addition, the hypothesis of self-medication has especially been suggested in cocaine abuse or dependence. Some limitations to this study can be discussed. First, although the recruitment was systematic and done in a public mental health service, the patients of our study are not necessarily representative of all schizophrenic patients. Secondly, as in any retrospective study, the prevalence of lifetime substance abuse may have been under-estimated. Urinary toxicology tests may have been able to improve the sensitivity of the diagnosis of recent substance abuse, but structured interviews are more appropriate for the diagnosis of lifetime substance abuse in schizophrenic patients than urinary toxicology tests. CONCLUSION: The socio-demographic characteristics of cannabis abuse or dependence in schizophrenia are similar to those found in general population. Cannabis using schizophrenic patients were more likely to be younger and male than non users. The duration of hospitalization was significantly longer for the group with cannabis abuse. Prevalence of suicide attempts in schizophrenia is closely correlated to cannabis abuse.

Absence of association between a polymorphic GGC repeat in the 5' untranslated region of the reelin gene and autism.

Autism is a complex neurodevelopmental disorder with severe cognitive and communication disabilities, that has a strong genetic predisposition. Reelin, a protein involved in neuronal migration during development, is encoded by a gene located on 7q22, within the candidate region on 7q showing increased allele sharing in previous genome scans. A case/control and family-based association study recently reported a positive association between a trinucleotide repeat polymorphism (GGC) located in the 5' untranslated region (UTR) of the reelin gene and autism. We performed a transmission disequilibrium test (TDT) analysis of the 5'UTR polymorphism in 167 families including 218 affected subjects (117 trios and 50 affected sib pairs) and found no evidence of linkage/association. Our results do not support previous findings and suggest that this GGC polymorphism of the reelin gene is unlikely to be a major susceptibility factor in autism and/or genetic heterogeneity.

[Predictive factors of response to buprenorphine in the substitutive treatment of heroin addicts. Results of a multicenter study of 73 patients]. / Facteurs prédictifs de la réponse à la buprénorphine en traitement substitutif des héroïnomanies. Résultats d'une étude multicentrique sur 73 patients.

OBJECTIVE: Buprenorphine has a partial morphine-agonist pharmacological profile. It is proposed as alternative to methadone in opiate drug addicts with greater safety of use and less cost in terms of public health. The aim of this study was to determine the clinical factors of response to this molecule. METHOD: The study was conducted in 73 patients treated for 3 months with adaptable doses. Mean dose was 8.5 mg/d (range: 3 to 16 mg/d). Response to treatment was defined as: still in the study at 3 months and absence of opiates in 75% of urinary samples over the past month. RESULTS: Forty-eight patients responded and 25 did not. The determinating clinical variables of response were: opiate drug addiction less than 10 years, high score on the Addiction Severity Index (ASI), absence of depression according to the Minnesota Multiphasic Personality Inventory (MMPI) and low rate of disinhibition on Zukerman's sensation seeking scale. Conversely, the dose of buprenorphine within the limits specified in the Marketing Authorisation did not intervene in the response. CONCLUSION: In view of its partial agonist effect, administration of buprenorphine must be reserved for patients addicted to opiates for less than 10 years, non-depressive and with low disinhibition on Zukerman's scale.

[French validation of a Minor Morphologic Anomalies Scale in schizophrenic patients and their parents]. / Validation française d'une échelle d'Anomalies Morphologiques Mineures appliquée à des patients schizophrènes et à leurs parents.

UNLABELLED: Minor Physical Anomalies represent valuable indices of disturbance in early neurodevelopment. They are frequently observed in individuals with various brain disorders, including mental retardation, autism, epilepsy, hyperactivity, foetal alcohol syndrome and schizophrenia. The high prevalence of Minor Physical Anomalies in schizophrenia provides considerable support for a neurodevelopmental model in this disorder. However, studies in large sample using standardised scale are lacking. Such studies are needed in order to confirm their actual frequency and study the clinical correlates or morphological anomalies. OBJECTIVE: The aim of this study was to revise and validate a French version of a scale designed for the evaluation of Minor Physical Anomalies in adult psychiatric patients and notably in patients with schizophrenia. METHODOLOGY: The scale was revised from the Waldrop scale. The choice of items was done on the basis of frequency, reliability in the adult, reliability of rating. Some new items, related to know syndroms with comportmental symptoms were added. Both raters had previously had a short initiation to the rating of the scale. Interrater reliability between two examiners, blind with regards to the diagnosis was evaluated. RESULTS: The interrater reliability was good, with an intraclass correlation coefficient at 0.97. Patients had significantly more minor physical anomalies than comparison subjects, and also more Minor Physical Anomalies than their parents. Fathers and mothers of these schizophrenic patients had significantly more Minor Physical Anomalies than normal comparison subjects. CONCLUSION: Although the evaluation of physical anomalies relies on subjective appreciation of normal vs abnormal, the revised version of minor physical anomalies scale (French version) was found to be a reliable tool, provided that a short initiation to the rating is performed. The scale differentiated schizophrenic patients from their parents, and the latter from the normal controls. A lot of questions remains unanswered concerning the neurodevelopmental hypothesis of schizophrenia. This scale appeared as a useful complementary tool to help in the determination of the developmental phenotypic status of the patients enrolled in pathophysiological studies aiming the identification of developmental factors in schizophrenia.

Impairment of predictive saccades in schizophrenia.

Using infrared oculography, we compared saccades toward predictable and pseudo-random visual targets in 19 neuroleptic-free patients with schizophrenia (including 13 neuroleptic-naïve patients) and in 29 age- and gender-matched healthy volunteers. Externally driven saccades were not different between patients and controls, whether or not the target was predictable. Anticipated saccades were specifically less accurate in the patients compared to the controls. The difference between primary gain of anticipated and non-anticipated saccades was markedly higher in the patients compared to controls (p=0.003). These results point to a deficit in the early step of internally driven oculomotor planning in schizophrenia.