[Principles of cognitive remediation in schizophrenia]. / Les principes de la remédiation cognitive dans la schizophrénie.

Cognitive remediation is an innovative psychosocial therapy which can provide a substantial benefit, especially for schizophrenic patients. As its name implies, the aim of cognitive remediation is to restore cognitive functions. Most cognitive domains (attention, memory and executive functions) are impaired in schizophrenia. Remediation therapy must be administered by an expert, and is based on cognitive training on the one hand, and on learning of cognitive strategies on the other hand. With these techniques the patient is better able to solve complex cognitive problems and to apply these new skills to everyday situations. Several techniques are available in France, using either computer-based or paper/pencil approaches. The programs are administered over several months, with one or more sessions per week. Cognitive remediation itself provides only a modest cognitive benefit, which must be enhanced by the adjunction of other therapies such as behavioral therapy, learning of social skills, or a vocational program during the first months of employment.

Variable individual sensitivity to cannabis in patients with schizophrenia.

There is now compelling evidence that cannabis consumption might precipitate psychosis onset. The objective of the present study was to assess the role of individual sensitivity to the psychotogenic effect of cannabis in male patients with schizophrenia. The lifetime diagnosis, disease and substance-use history were determined using a standardized interview in 190 patients with schizophrenia. Of patients with lifetime cannabis use (n=121), 44 were characterized as Cannabis-sensitive (CS) patients if the onset of psychotic symptoms occurred within 1 month following the initiation of cannabis consumption, or following a marked rise of cannabis consumption, or marked aggravation of psychotic symptoms each time the subject used cannabis. Age at onset of psychosis was not different in patients with lifetime cannabis use compared to non-users. By contrast, the first psychotic episode occurred 2.6 yr earlier in CS compared to Non-cannabis-sensitive (NCS) patients (p=0.006). Moreover, a specific excess of family history of psychotic disorder was found in CS patients, but not of any other psychiatric disorder, as well as an earlier age at exposure to cannabis (16.7+/-2.5 yr, p=0.03). Sensitivity to psychotogenic effects of cannabis in schizophrenia patients could be related to both genetic vulnerability to schizophrenia and the influence of cannabis on brain maturation and could modulate the influence of cannabis on the onset of schizophrenia.

Maintenance electroconvulsive therapy: an alternative treatment for refractory schizophrenia and schizoaffective disorders.

This retrospective chart review of a clinical cohort of 19 refractory schizophrenic or schizoaffective patients treated with maintenance electroconvulsive therapy addresses the indications for this treatment, its efficacy, and its impact on daily functioning and hospitalizations. Maintenance electroconvulsive therapy combined with medication appears to be an efficient alternative to pharmacological treatment alone.

Deficit of inhibition motor control in untreated patients with schizophrenia: further support from visually guided saccade paradigms.

In addition to classical delusional, negative, and cognitive deficit, schizophrenia has consistently been associated with impairments in saccadic eye movements, e.g., an increased error rate in the antisaccade task. We hypothesized that a deficit in inhibitory control is a core defect in untreated patients with schizophrenia leading to impairment in different oculomotor paradigms. Ten drug-free or drug-naïve patients with schizophrenia were matched in age and gender to 11 healthy controls with no psychoactive substance use or abuse. They were explored using reflexive saccades with unpredictable targets with or without the gap procedure, predictive saccades and a fixation/distracter paradigm. Patients with schizophrenia displayed shorter latency in reflexive and predictive saccades. In the GAP condition, patients made more anticipatory saccades, fewer regular saccades, and had a shorter latency of express saccades than controls. In addition, patients had an increased error rate in the fixation/distracters task. Altogether, these results provide new evidence of reduced prefrontal inhibitory regulation of subcortical and brainstem systems involved in the control of saccades.

[Forensic psychiatry]. / 'Un état des lieux de l'expertise psychiatrique au pénal.

CURRENT SITUATION: in France about 700 psychiatrists are licensed to determine criminal responsibility before the courts, in other words to assess whether a criminal was capable of knowing what he or she was doing or of controlling him or herself Criminals who are considered irresponsible are committed to psychiatric hospitals. Criminals who are considered to have diminished judgment or control may nonetheless be prosecuted and jailed Psychiatric experts may also be asked to predict aggressive behaviour, and to identify determinants of crime. Too often the answers are not fully grounded in science, and this is not made sufficiently clear. There are 26 psychiatric wards in French prisons, which only treat inmates who accept to be treated. When prisoners are prescribed compulsory treatment, they are discharged from prison and transferred to a psychiatric ward. This situation is more and more frequent but is not the most convenient: it delays treatment and does not facilitate long-term therapeutic relationships. Responsibility or pragmatism? About 20% of French prison inmates are psychotic, and these individuals are at risk of repetitive violent behaviour if left untreated. The main question is not one of criminal responsibility, but rather the most effective response to antisocial behaviour: is punishment or medical treatment the most effective way of preventing future crimes and protecting society? Ethical aspects: the situation could be improved by a number of measures. For example, training in forensic psychiatry should be obligatory before accreditation before a Court, and psychiatric diagnoses should be based systematically on the ICD10. Psychiatrists have a special duty to inform on advances and uncertainties in their field, in terms of diagnosis, prognosis and treatment.

The French version of the validated short TEMPS-A: the temperament evaluation of Memphis, Pisa, Paris and San Diego.

The TEMPS developed from classical temperament concepts at the Universities of Tennessee (Memphis) and California (San Diego) in collaboration with clinical scientists in Pisa and Paris. It presently exists in 20 languages and full validation of its 110-item version has been accomplished in American English, Italian, French, German, Hungarian, Japanese, Turkish, Lebanese Arabic and Argentinean Spanish. For many studies, a shorter version is easier to use. Accordingly, the 39-item validated English version has just been rendered into French, to facilitate clinical use and research in Francophone countries.

Augmentation strategies of clozapine with antipsychotics in the treatment of ultraresistant schizophrenia.

BACKGROUND: Approximately 40% to 70% of neuroleptic-resistant schizophrenic patients are nonresponders to clozapine. Several clozapine augmentation strategies have come into clinical practice although often without evidence-based support. Among these strategies, the combined use of clozapine with another antipsychotic has been reported for up to 35% of patients receiving clozapine. OBJECTIVE: The purposes of the present work were to (1) review the available literature on the efficacy and safety of the clozapine augmentation with another antipsychotic using a MEDLINE search of the literature from 1978 to December 2005 and (2) to propose an operational definition of schizophrenia refractory to clozapine ("ultraresistant schizophrenia") for the implementation and homogenization of future therapeutic trials. CONCLUSION: Case controls and open clinical trials largely dominate the literature, and there are only 4 double-blind studies of clozapine augmentation with antipsychotics. The results of these studies are somewhat discrepant. Moreover, the heterogeneity of definitions of resistance to clozapine, of outcome measures and of dose and duration of pharmacological trials is a major limitation for drawing conclusions.

Somatic augmentation strategies in clozapine resistance--what facts?

BACKGROUND: Polypharmacy without evidence-based support is sometimes needed for patients treated with 40% to 70% clozapine who are clozapine nonresponders. Several somatic augmentation strategies are proposed in the scientific literature, with different levels of evidence for safety and efficacy. OBJECTIVES: The purpose of the present study is to review the available literature on the efficacy and safety of clozapine augmentation with somatic agents other than antipsychotics. The following classes of agents are considered: (1) mood stabilizers, (2) antidepressants, (3) electroconvulsive therapy and repetitive transcranial magnetic stimulation, (4) glutamatergic agents, (5)fatty acids supplements, and (6) benzodiazepines. RESULTS: Case controls and small-size clinical trials largely dominate the literature, limiting the power to draw conclusions concerning safety issues and the meaning of negative studies. Moreover, variable definitions of clozapine resistance, heterogeneous outcome measures, and short duration of treatment trials are additional limitations. CONCLUSION: Generally, adjunctive strategies for clozapine-resistant patients remain based on scarce evidence of efficacy and significant safety concerns. Low-frequency repetitive transcranial magnetic stimulation, fatty acids supplements, and mirtazapine showed good tolerability and some efficacy, but the results need replication.

[Physiological adolescence, pathological adolescence]. / Adolescences physiologiques, adolescences pathologiques.

The uncertainties of looming adulthood, nostalgia for childhood, and a general malaise explain the crisis of adolescence. Rebellion, conflict, occasional failure at school or in society, and at-risk behaviors are not always signs of future psychiatric illness. In contrast, the physician must be in a position to identify tell-tale signs such as dysmorphophobia, existential anxiety, a feeling of emptiness, and school or social breakdown. Most psychiatric disorders that begin in adolescence are only diagnosed several years after onset. Yet early diagnosis is of utmost importance, as treatment becomes less effective and the long-term prognosis worsens with time. Suicide is the second cause of death during adolescence. All signs of suicidal behavior require hospitalization and evaluation in a psychiatric unit. Antidepressants may be necessary in adolescence. The recent controversy concerning a possible increase in the suicidal risk during antidepressant treatment should not mask the fact that the real public health issue is depression, and not antidepressants. Eating disorders are especially frequent among adolescent girls; it is important to identify psychiatric comorbidities such as schizophrenia, depression and obsessive-compulsive disorders, and to assess the vital risk. Illicit drug and alcohol consumption are frequent during adolescence; for example, close to half of all French adolescents have tried cannabis at least once. Once again, it is important to detect psychiatric comorbidities in substance-abusing adolescents. Phobia is an underdiagnosed anxiety disorder among adolescents; it may become chronic if proper treatment is not implemented, leading to suffering and disability. Finally, two major psychiatric disorders--schizophrenia and bipolar disorder--generally begin in adolescence. Treatment efficacy and the long-term prognosis both depend on early diagnosis. Treatment must be tailored to the individual patient. "Borderline" states are over-diagnosed, hindering more precise diagnosis and delaying appropriate treatment.

Cognitive dysfunctions in medicated and unmedicated patients with recent-onset schizophrenia.

Schizophrenia is associated with impairments in many cognitive domains on which the influence of antipsychotics, whether conventional or atypical, remains unclear. We conducted a study of recent-onset schizophrenic patients (DSM IV) that included unmedicated (n=19), and medicated (n=19) patients matched for age and IQ. Both groups of patients had comparably low extra-pyramidal symptoms (EPS). Cognitive tasks included attentional tasks (alertness and divided attention tests), a working memory task (a verbal n-back test) and the Wisconsin Card Sorting Test (WCST). After adjustment for the Total PANSS score, we found no significant difference between the two groups of patients in any of the cognitive tasks. When compared to a group of healthy controls (n=20) matched for IQ level, unmedicated patients performed significantly worse in all cognitive tasks, with significantly longer reaction times for alertness, divided attention and working memory. These results confirm the presence of cognitive impairments in attentional and executive functions in recent-onset patients whether or not they are medicated. There was no evidence that either conventional or atypical antipsychotics had an influence on patients when EPS were excluded. Altogether, our results further support the idea that cognitive deficits in schizophrenia are enduring features per se and cannot be considered as secondary to psychiatric symptoms or to the adverse effects of medication. In addition our results suggest that antipsychotics do not have a major effect on these impairments.

[Stress, depression and cerebral plasticity: an update of clinical and experimental findings]. / Stress, dépression et plasticité cérébrale: mise au point a partir des etudes cliniques et expérimentales.

Recent studies of neuroplasticity in stress and depression have given rise to new hypotheses on the neural bases of these disorders. Based on data from imaging studies, cellular and molecular biology, and animal models, this approach could help to understand certain clinical findings, and especially cognitive impairments. Some antidepressants have effects on neuroplasticity, in addition to their symptomatic effects on depression.

[Schizophrenic disorders: current etiologic and clinical knowledge]. / Schizophrénies: actualités etiopathogéniques et cliniques.

Brain anomalies associated with schizophrenic disorders may be of a cognitive, neurophysiological or neurological nature [the latter being relatively minor and nonspecific]. Brain imaging has revealed early anomalies such as cortical-subcortical atrophy and abnormal gyration. These anomalies can also be present in relatives free of schizophrenic symptoms. This raises the question of what determines the transition from vulnerability to clinical onset. There is now evidence that schizophrenic disorders are true brain diseases. This is based on neuropathological studies, brain imaging and clinical findings such as "soft" neurological signs (pyramidal and extrapyramidal symptoms, coordination difficulties, etc.). Cognitive dysfunctions such as attention and memory disorders and abnormal verbal fluency have also been described. Oculomotor pursuit and auditive evoked potentials have identified specific neurophysiological disorders such as N300 and P50 wave modifications. Schizophrenic disorders can also be associated with neuronal abnormalities, notably affecting factors involved in synaptic transmission and plasticity. For example, BDNF protein deficit is linked to certain late-onset forms of schizophrenia. Genetic studies are no longer focusing on a possible disease genotype but rather on phenotypic characteristics determined by simpler genotypes (P50 wave modulation, COMT and BDNF genes). The ultimate objective is to identify high-risk subjects, in order to shorten the treatment delay and thereby improve long-term outcome. The benefit of primary prophylaxis remains to be determined, however.

[Early clinical signs of dementia in the elderly]. / Les signes cliniques précurseurs d'un processus démentiel chez le sujet agé.

Clinical signs and symptoms preceding the onset of dementia are sometimes acute, such as mood disorders often associated with hypochondriacal traits and cognitive slowing, sudden and serious suicide attempts, character and conduct disorders contrasting with the previous state, and psychotic disorders presenting as pathological mistrust, or ill-structured prejudice or persecution. Most forerunning symptoms reflect a progressive deterioration of cognitive functions over a long period, that have been masked by various coping strategies used by the patient with the spouse's help. Progressive cognitive deficits may develop over years before dementia can be diagnosed with confidence. Quantitative tools can help to detect dementia incipiens, such as the Folstein Mini Mental Test, the Mattis Dementia Scale, the five-word learning test, the clock drawing test, and the brief cognitive battery. The profile of early cognitive deterioration varies according to the type of dementia (Alzheimer's disease, fronto-temporal dementia, Lewy body dementia, and vascular dementia). The symptoms of dementia may be interlinked with symptoms of other disorders. Neuropsychological tests and brain imaging are needed to validate the diagnosis.

A double-blind, randomized comparative trial of amisulpride versus olanzapine for 6 months in the treatment of schizophrenia.

Atypical antipsychotics offer advantages over earlier drugs for the treatment of schizophrenia, although few data exist on the relative merits of different atypical antipsychotics. A multicentre, double-blind, randomized trial was performed to compare amisulpride and olanzapine in the treatment of acute schizophrenia. Adult schizophrenic patients with dominant positive symptomatology received amisulpride (200-800 mg/day) or olanzapine (5-20 mg/day) for 6 months. The primary efficacy variable was change from baseline of the Brief Psychiatric Rating Scale (BPRS) score, assessed with a non-inferiority analysis. The evolution of positive and negative symptomatology, depression, social functioning and quality of life were assessed. Safety evaluation included adverse event reporting, neurological status and body weight. The improvement of BPRS score was 32.7% in the amisulpride group and 33.0% in the olanzapine group; thus, the efficacy of amisulpride was not inferior to that of olanzapine. All other secondary efficacy outcome variables evolved to a similar extent in both groups. Adverse event frequency was similar in both groups. Amenorrhoea was encountered only in the amisulpride group (6.2% of patients), whereas elevations of liver transaminases were more frequent in the olanzapine group (17% versus 3.7% of patients). The incidence and mean extent of clinically relevant weight gain were higher in the olanzapine group (35.1% and 3.9 kg) than in the amisulpride group (20.6% and 1.6 kg). The efficacy of amisulpride is not inferior to that of olanzapine in the treatment of acute schizophrenia. The side-effect profile of the two drugs differed.

Minor physical anomalies in patients with schizophrenia and their parents: prevalence and pattern of craniofacial abnormalities.

The frequency of minor physical anomalies (MPAs) in patients with schizophrenia suggests an early disturbance in the development of the neuroectoderm. To improve the phenotypic delimitation of this disorder, we used a comprehensive scale of MPAs (41 items) in patients with schizophrenia and their first-degree relatives. This scale, adapted from a revised version of the Waldrop Scale (Ismail et al. Minor physical anomalies in schizophrenic patients and their siblings, American Journal of Psychiatry 155, 1998a, 1695-1702), introduced new items assessing facial and limbs asymmetry. The interrater reliability between two examiners was good: intraclass correlation coefficient: 0.68 (0.42-0.92). Patients with schizophrenia (n=40; mean=5.8, S.D.=4) and their non-psychotic parents (n=45; mean=4.7, S.D.=2.8) had significantly more MPAs than healthy comparison subjects (n=42; mean=2.2, S.D.=1.2). A logistical regression model showed the ability of several items to predict group status, including facial asymmetry, cleft palate, hair whorls and abnormal palmar crease. The high prevalence of facial asymmetry in patients with schizophrenia and their first-degree relatives provides new insights into the underlying dysembryogenic processes. This revised scale thus appears to be a useful complementary tool in pathophysiological studies aiming at the identification of developmental factors in schizophrenia.

Correlation between clinical syndromes and neuropsychological tasks in unmedicated patients with recent onset schizophrenia.

The aim of this study is to circumscribe the cognitive deficits according to schizophrenic syndromes in a population of sub-acute untreated patients. We have studied the cross-sectional correlation between cognitive deficits and schizophrenic symptoms, in a group of 24 untreated patients (including 17 neuroleptic-naive patients) with recent onset of the disease. A task of alertness, a working memory (WM) test (including two levels of difficulty) and an abbreviated version of the Wisconsin Card Sorting Test (WCST) were selected. WM deficits and poor performance on the WCST were highly correlated with disorganized symptoms, modestly with the positive syndrome and not with the negative syndrome. Thus, disorganized symptoms, more than any other, appear to be related to the impairment of executive function and WM in recent onset unmedicated patients with schizophrenia.

[Depression and aging]. / Dépression et vieillissement.

Depression is one of the most common health disorders in elderly people. It is still often considered as a natural consequence of aging, arising in reaction to a medical disease, cognitive or functional decline, or a loss of social fabric. Many studies have highlighted the low rates of diagnosis and treatment of depression, especially in the primary care setting. Major depression in old age is characterized by the same core symptoms as in other periods of life. However, aging may accentuate some symptoms and alleviate others. Somatic concern, marked anxiety, poor subjective memory, psychotic ideation, and recurrent thoughts of death can mask sadness and anhedonia. Organic factors and adverse life events are often intricately linked with the pathogenesis of depressive states in the elderly. The role of cerebrovascular lesions has also been established, particularly in late-onset depressive disorders. The management of depressive disorders in older people, as in younger adults, involves pharmacological and psychological treatments. Electroconvulsive therapy can be beneficial in some cases. Transcranial magnetic stimulation is being evaluated in this setting.

Confirmation of the factorial structure of temperamental autoquestionnaire TEMPS-A in non-clinical young adults and relation to current state of anxiety, depression and to schizotypal traits.

BACKGROUND: The 39-item TEMPS-A self-rated questionnaire assesses affective temperaments. We examined the factorial structure of its French version in a large sample of young adults and examined the relation to schizotypy, depression and anxiety. METHOD: University students were enrolled during their mandatory preventive health visit in the University medical facility (n = 3807, 19.9 ± 2.5 y.o.). They answered to the 39-TEMPS-A questionnaire, the Schizotypal Personality Questionnaire (SPQ) and the Hospital Anxiety Depression Scale (HADS). We performed an exploratory Factorial Component Analysis (FCA) with varimax rotation of the 39-TEMPS-A in half of the sample, randomly selected, followed by a Confirmatory Factor Analysis (CFA) in the remaining subsample. TEMPS-A dimensions were correlated to HADS and SPQ sub-scores. RESULTS: A five-factor structure was found by PCA and confirmed by the confirmatory analysis. The scale showed a good internal consistency (whole scale Cronbach's α: 0.83 and from 0.78 to 0.59 for Cyclothymic, Depressive, Irritable, Hyperthymic, Anxious subscales). Depressive and Anxious TEMPS-A subscales were moderately correlated to HADS Depression and Anxiety subscales (Spearman ρ = 0.37 to 0.33). Cyclothymic and Depressive TEMPS-A subscales were respectively correlated to SPQ Paranoid (ρ = 0.53) and Negative dimensions (ρ = 0.52). LIMITATION: Representativity of the sample (higher education, response rate). CONCLUSION: We confirmed the five factor structure of the 39-item TEMPS-A in a large non-clinical population of young adults and found consistent correlations with anxiety - depression state markers and schizotypal traits.