[Plasmatic glutathione levels and their relationships with clinical and therapeutic features in patients with schizophrenia]. / Concentrations plasmatiques des glutathions et leurs corrélations avec les caractéristiques cliniques et thérapeutiques des patients atteints de schizophrénie.

INTRODUCTION: Altered glutathione systems (GSH) are suggested to participate in the pathophysiology of schizophrenia. The purpose of this study was to determine the plasmatic glutathione levels of patients with schizophrenia compared to healthy controls and to examine their relationships with clinical and therapeutic features. METHODS: It was a case-control study carried out on 100 patients with schizophrenia according to DSM-IV-TR criteria and 95 healthy controls. All patients were assessed by Clinical Global Impressions-severity (CGI-severity) and Global Assessment of Functioning (EGF). Most of the patients (55%) were under first-generation antipsychotics. Plasmatic glutathione levels (total glutathione GSHt, reduced glutathione GSHr, oxidized glutathione GSSG) were determined by spectrophotometry. RESULTS: The levels of GSHt and GSHr were significantly decreased in schizophrenic patients in comparison with the healthy controls. These reductions were noted to be more pronounced in the untreated patients. No correlation was observed between the GSH levels and the clinical subtypes of schizophrenia and EGF scores. Depending on the therapeutic status, there were no significant differences in the GSH levels. In addition, there was no correlation between the GSH levels and the daily dosage of the antipsychotic treatment. CONCLUSION: Our results suggest that the observed changes are related to the physiopathology of schizophrenia rather than to the presence of neuroleptic treatment. These results provide support for further studies of the possible role of antioxidants as neuroprotective therapeutic strategies.

[Symptomatic remission and its relationship to social functioning in Tunisian out-patients with schizophrenia]. / Rémission symptomatique et sa relation avec le fonctionnement social chez des patients tunisiens suivis pour schizophrénie.

INTRODUCTION: The concept of symptomatic and functional remission represents an important challenge in the care of the mentally ill, particularly in patients with schizophrenia. Operational criteria for symptomatic remission in schizophrenia have been proposed by Andreasen et al. (2005). Over the last decade, these criteria have been widely validated; however few studies have been conducted outside developed countries. Moreover, the association of symptomatic remission with functional outcome has not yet been established in developing countries including Tunisia, as there may be variability in the social and familial environment. OBJECTIVES: To determine the frequency and associated factors of symptomatic remission in a sample of Tunisian out-patients with schizophrenia and to explore the relationship between symptomatic remission and some indicators of social functioning. METHODS: A cross-sectional study was carried-out on 115 out-patients with schizophrenia (87 males, 28 females, mean age=37.56±10.2 years) in the psychiatry department of the university hospital in Monastir (Tunisia). Nearly all of the patients (98.26%) had been hospitalized at least once in a psychiatric unit. The last hospitalization dated back to 39 months on average (range=6 months to 16 years). Symptomatic remission was assessed by the eight core items of the positive and negative syndrome scale (PANSS). These are the items P1 "Delusions"; P3 "Hallucinatory behavior" and G9 "Unusual thought content" for the positive dimension, the items P2 "Conceptual disorganization" and G5 "Mannerism and disorders of posture" for the disorganization dimension and the items N1 "Blunted affect", N4 "Social withdrawal" and N6 "Lack of spontaneity and flow of conversation" for the negative dimension. A score of mild or less on all eight-core symptoms constitutes symptomatic remission. This symptom level should have been maintained for six months. The social functioning was assessed by the Social and Occupational Functioning Assessment Scale (SOFAS) and the Social Autonomy Scale (SAS) exploring personal care, management of daily life, resource management, the relationship with the outside and the emotional life and relationships social. A multivariate analysis using a binary logistic regression was conducted with as a dependent variable "symptomatic remission" and as explanatory variables the associated variables with symptomatic remission in bivariate analysis with age and gender. RESULTS: The symptomatic remission was observed in 50.4% of patients. The items corresponding to positive dimension (P1, P3 and G9) and the item P2 "conceptual disorganization" had a better predictive value of symptomatic remission. After multivariate analysis, the associated factors of symptomatic remission were the acute of onset (P=0.026), the low score of negative symptoms during the last hospitalization (P=0.017) and the episodic course (P<0.0001). However, age or gender of the patients, educational or socioeconomic level, psychiatric family history, age of onset, duration of untreated psychosis, number and duration of previous hospitalizations, antipsychotic treatment dosage were not associated with symptomatic remission in our sample. The mean score of the SOFAS was 48.47±14.44, and the mean score of the SAS was 56.6±16.84. A significant association was shown between the SOFAS score and the symptomatic remission (P<0.0001) and between the SAS score and the symptomatic remission (P<0.0001). Moreover, a significant association was found between symptomatic remission and occupational activity (P=0.03). CONCLUSION: The frequency of symptomatic remission according the PANSS criteria in our sample is above the average of the reported rates in literature (30 to 60%). This can be explained by the frequency of symptomatic remission in outpatient versus inpatients, or in relation to the notion of a more favorable course of schizophrenia in developing countries, although this notion is controversial. Remitter patients had significantly an acute onset of disorders, a low score of negative symptoms during the last hospitalization and an episodic course. They also showed a significant trend for better social functioning. In fact, a significant association was shown in our sample between symptomatic remission and social functioning. These results suggest that the concept of remission has important implications for the treatment of patients with schizophrenia.

The structure of schizotypal personality traits: a cross-national study.

BACKGROUND: Schizotypal traits are considered a phenotypic-indicator of schizotypy, a latent personality organization reflecting a putative liability for psychosis. To date, no previous study has examined the comparability of factorial structures across samples originating from different countries and cultures. The main goal was to evaluate the factorial structure and reliability of the Schizotypal Personality Questionnaire (SPQ) scores by amalgamating data from studies conducted in 12 countries and across 21 sites. METHOD: The overall sample consisted of 27 001 participants (37.5% males, n = 4251 drawn from the general population). The mean age was 22.12 years (s.d. = 6.28, range 16-55 years). The SPQ was used. Confirmatory factor analysis (CFA) and Multilevel CFA (ML-CFA) were used to evaluate the factor structure underlying the SPQ scores. RESULTS: At the SPQ item level, the nine factor and second-order factor models showed adequate goodness-of-fit. At the SPQ subscale level, three- and four-factor models displayed better goodness-of-fit indices than other CFA models. ML-CFA showed that the intraclass correlation coefficients values were lower than 0.106. The three-factor model showed adequate goodness of fit indices in multilevel analysis. The ordinal α coefficients were high, ranging from 0.73 to 0.94 across individual samples, and from 0.84 to 0.91 for the combined sample. CONCLUSIONS: The results are consistent with the conceptual notion that schizotypal personality is a multifaceted construct and support the validity and utility of SPQ in cross-cultural research. We discuss theoretical and clinical implications of our results for diagnostic systems, psychosis models and cross-national mental health strategies.

[Minor neurological and physical anomalies in patients with first-episode psychosis]. / Anomalies neurologiques et physiques mineures chez des patients présentant un premier épisode psychotique.

INTRODUCTION: Over the last several decades, there has been an increasing number of neuroanatomical, neuroimaging, neurophysiological, and neuropsychological studies in search of structural, functional, and cognitive correlates of brain insult(s) that could ultimately lead to unravelling the pathophysiology of schizophrenia. A direct, easily administered, and inexpensive way of investigating brain dysfunction in schizophrenia is the study of neurological soft signs and minor physical anomalies, two putative indices of developmental abnormality. The study of these neurodevelopmental markers in the first-episode psychosis allows the detection of the neurodevelopmental abnormalities at the onset of psychosis. AIMS OF THE STUDY: The objectives of our study were to determinate the prevalence, the scores, and the nature of neurological soft signs (NSS) and minor physical anomalies (MPA) in patients with first-episode psychosis and to explore the correlations between these neurodevelopmental markers and the demographic, clinical and therapeutic features. METHOD: A cross-sectional study was carried-out on 61 patients (mean age: 28.9±9.4years; 86.9% were males), hospitalized for first-episode psychosis (DSM-IV-TR diagnosis of schizophrenia, schizophreniform disorder, brief psychotic disorder, delusional disorder, and psychotic disorder not otherwise specified). The evaluation procedure consisted of a retrospective assessment of the premorbid functioning by the Premorbid Functioning Scale (PAS) and the following clinical scales: Positive and Negative Symptoms Scale (PANSS), Clinical Global Impression (CGI) and Global Assessment of Functioning (GAF), the NSS scale of Krebs et al. (23 items exploring motor coordination, motor integrative function, sensory integration, involuntary movements or posture, quality of lateralization) and the MPA scale of Gourion et al. (41 items, exploring anomalies of face, eyes, ears, mouth, hands and feet). RESULTS: The prevalence of NSS was 83.6% (cut-off point=9.5), with a mean total score of 15.3±6.7. The highest score was for the motor coordination. The prevalence of MPA was 62.7% (cut-off point=5), with a mean total score of 5.8±3.2. The most common MPA were the fine hair (50.8%), adherent earlobes (49.2%) and clinodactyly (31.1%). Correlations were found between the NSS total score and the Poor Premorbid Functioning (r=0.32, P=0.04), the PANSS total score (r=0.36, P=0.005), and the negative (r=0.45, P<0.001) and disorganization sub-scores (r=0.41, P=0.001), the CGI-severity of (r=0.30, P=0.02), the impairment functioning in the GAF (r=-0.26, P=0.04) and with extrapyramidal symptoms (r=0.52, P<0.001). However, no correlation was found between the NSS total scores, age, gender, the PANSS positive sub-score, the daily dosage of antipsychotics, the CGI-improvement score and the MPA total score. There was no correlation between MPA total score and demographic, clinical and therapeutic features of patients. Moreover, there was no correlation between the NSS or MPA scores and the short-term evolution (6months to 1year) towards schizophrenia. CONCLUSION: These results confirm the data in the literature relating high NSS and MPA scores in patients with a first-episode psychosis. The NSS appear to characterize severe psychotic disorders with more negative and disorganization symptoms and poor social functioning and may be a prognostic indicator.

[Hyperhomocysteinemia and schizophrenia: case control study]. / Hyperhomocystéinémie et schizophrénie : étude cas-témoin.

OBJECTIVES: Homocysteine (Hcys) is a sulphur-containing amino acid that has been widely investigated for its putative role in neuropsychiatric disorders. Elevated plasma homocysteine levels have been associated with schizophrenia. Among other factors, low folate and vitamin B12 levels have been implicated in the increase in homocysteine. The aim of the study was to determine plasma Hcys, folate and vitamin B12, and the frequency and severity of hyperhomocysteinemia in patients with schizophrenia, and to investigate the association between Hcys and clinical features and its relationship with folate and vitamin B12 levels. METHODS: This was a case-control study carried out on 61 (54 males and seven females, mean age=33.3 ± 9.2) inpatients with chronic schizophrenia according to DSM-IV criteria and 46 (25 males and 21 females, mean age=45.9 ± 14.2) healthy controls. Most of patients (90.2%) were treated by first generation antipsychotics with a mean daily dosage of 401.6 mg chlorpromazine equivalents. Total homocysteine serum levels were determined quantitatively by fluorescence-polarization immunoassay (FPIA) with an AxSYM analyzer™ (Abbott). Quantitative vitamin B12 and folate serum levels were measured with an Elecsys 2010 analyzer™ (Roche Diagnostics). Differences between patients and controls were examined using a two-way Ancova with gender and diagnosis as independent variables, adjusting for age. RESULTS: Patients with schizophrenia showed higher plasma Hycs and lower plasma folate than controls (mean=16.1 µmol/L in patients versus 10.9 µmol/L in controls; P=0.028 for Hycs and 4.2 µg/L in patients versus 8.2 µg/L in controls; P<0.001 for folate). Patients and controls did not differ in vitamin B12 levels. Both male and female patients had increased plasma Hcys compared to controls. Hyperhomocysteinemia (Hcys levels>15 µmol/L) was present in 34.4% of the patients versus 15.2% in controls. The prevalence of moderate hyperhomocysteinemia (Hcys levels: 15-29 µmo/L) was 26.2% and that of intermediate hyperhomocysteinemia (Hcys levels: 30-100 µmol/L) was 8.2%. In patients with schizophrenia, plasma Hcys was not correlated with age (r=0.07; P=0.56), duration of illness (r=-0.04; P=0.78) and did not differ with gender and clinical sub-types. Moreover, plasma Hcys was higher in patients without family history of psychiatric disorders (19.2 µmol/L) versus 12.7 µmol/L in patients with family history of psychiatric disorders (P=0.032). Concerning therapeutic features, plasma Hcys did not differ with type of antipsychotic and was not related to daily dosage of antipsychotics. A negative correlation was found between plasma Hcys and vitamin B12 levels (r=-0.26; P=0.04). CONCLUSION: These results confirm an increase of Hcys levels in schizophrenic patients and suggest that it is associated with absence of family history of psychiatric disorders and with low vitamin B12 levels. Hyperhomocyteinemia could be related to the pathophysiology of aspects of this illness. Homocysteine should be considered as a factor to consider in monitoring and management of patients with schizophrenia.

Metabolic syndrome in Tunisian bipolar I patients.

BACKGROUND: The metabolic syndrome is a growing global public health problem which is frequently associated with psychiatric illness. OBJECTIVES: To evaluate the prevalence of metabolic syndrome and to study its profile in Tunisian bipolar I patients. METHODS: Our study included 130 patients with bipolar I disorder diagnosed according to the DSM-IV and assessed for metabolic syndrome according to the National Cholesterol Education Program (NCEP) Adult Treatment Panel (ATP) III modified criteria. The mean age was 37.9 ± 12.1 years, 45 were women (mean age 37.5 ± 13.4 years) and 85 were men (mean age 38.1 ± 11.4 years). RESULTS: The prevalence of metabolic syndrome was 26.1%.The highest prevalence of this syndrome was obtained by association between obesity, low c-HDL and hypertriglyceridemia (44.1%). In the total sample, 59.2% met the criteria for low c-HDL, 53.1% for hypertriglyceridemia, 33.8% for obesity, 16.1% for high fasting glucose and 5.4% for hypertension. Gender, age, illness episode and treatment were not significantly associated with metabolic syndrome, while patients under lithium had higher prevalence of metabolic syndrome than those under valproic acid, carbamazepine or antipsychotics. Patients with metabolic syndrome had significant higher levels of HOMA-IR and uric acid than metabolic syndrome free patients (p< 0.001). CONCLUSIONS: Bipolar patients have high prevalence of metabolic syndrome which is associated with insulin resistance and an increase of uric acid values that raise the risk of cardiovascular disease.

[Affective temperaments in the bipolar and unipolar disorders: distinctive profiles and relationship with clinical features]. / Tempéraments affectifs dans les troubles bipolaires et unipolaires : comparaison des profils tempéramentaux et relation avec les caractéristiques cliniques.

INTRODUCTION: Recent research postulated that temperaments represent the subclinical foundations of affective disorders, and an early clue for a recurrent, prebipolar disorder. Akiskal et al. operationalized five types of temperaments: depressive, hyperthymic, irritable, cyclothymic and anxious. The aims of this study were to compare the affective temperaments scores in patients with bipolar I, II and recurrent depression disorders and to explore the relation between temperaments scores and clinical features of those affective disorders. METHODS: This was a comparative cross-sectional study, concerning three groups: patients with bipolar I disorder (BIP I) (n=31, 20 men and 11 women, mean age=42.0+/-10.1 years), patients with bipolar II disorder (BIP II) (n=18, 11 men and seven women, mean age=40.7+/-10.8 years) and patients with recurrent depressive disorder (RDD) (n=66, 28 men and 38 women, mean age=45.0+/-9.3 years). All patients were in remission of a major depressive episode. The affective temperaments were assessed by the Akiskal and Mallya Affective Temperament questionnaires. RESULTS: Hyperthymic temperament mean scores were higher in BIP I (10.8+/-5.4) and BIP II (10.3+/-5.5) groups compared to RDD group (5.5+/-4.0) (p<10(-3)). Depressive temperament mean score was significantly higher in RDD group (10.5+/-4.3), compared to BIP I (7.3+/-4.6) and BIP II (5.4+/-2.9) groups (p<10(-3)). Cyclothymic temperament mean score was higher in BIP II group (4.7+/-5.8) compared to BIP I (3.3+/-3.9) and RDD (2.5+/-3.9) groups, but this difference was not significant (p=0.08). No difference was found between the three groups concerning irritable temperament scores. Negative correlation was found between hyperthymic and depressive temperament scores in BIP I (r=-0.81, p<0.001) and RDD (r=-0.73, p<0.001) groups, but not in BIP II group. Concerning the clinical correlates with affective temperament scores, negative correlation was found between hyperthymic temperament score and number of depressive episodes in BIP II group (r=-0.53, p=0.02). Hyperthymic temperament score was associated with psychotic features in the last depressive episode in BIP I (p=0.01) and BIP II (p=0.008) groups and seasonal features in BIP II group (p=0.02). Moreover, cyclothymic temperament score was associated with psychotic (p=0.009) and seasonal features (p=0.03) in BIP II group. CONCLUSIONS: Despite the small sample sizes for our study groups, we can conclude that hyperthymic and cyclothymic temperaments characterized bipolar disorders and are correlated with other markers of bipolarity such as psychotic and seasonal features. Thus, temperament assessment might become a useful tool to predict bipolarity in association with those markers.

[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.

[Clinical characteristics of bipolar I patients according to their family history of affective disorders]. / Caractéristiques cliniques des patients bipolaires type I en fonction de leurs antécédents familiaux thymiques.

BACKGROUND: The familial nature of bipolar disorder has been well described and multiple genes are probably involved in most or all cases. Each gene contributes equally to a bipolar phenotype and it may contribute to clinical characteristics. However, the genetic transmission of bipolar disorder remained undetermined up to now, partly due to clinical and genetically heterogeneity. In Tunisia, genetic study will profit from specific interests and advantages: the high rates of consanguinity, the existence of large families, and the relative geographical stability of the population. OBJECTIVE: The aim of this study was to compare clinical characteristics of familial and nonfamilial bipolar I disorder. METHOD: One hundred and thirty subjects met DSM-IV criteria for a bipolar I disorder; they were recruited and divided into groups according to their family history of affective disorders. Group 1 with a familial history group, comporting bipolar I patients with a family history of affective disorders in first and second degree relatives (n = 76; 52 males and 24 females, mean age = 37.2 +/- 10.7 years) was compared to group 2 (nonfamilial history group), comporting bipolar I patients without a family history of affective disorders (n = 54; 29 males and 25 females, mean age = 38.1 +/- 10.9 years). Available information was obtained from a structured clinical interview, collateral history, and medical records. The family investigation permitted completion of genealogies over three generations. The comparison of the two groups was based on the clinical characteristics (age at onset, numbers of affective episodes, nature and severity of the last affective episode,...). RESULTS: There were no significant differences between the two groups concerning demographic and social features, with the exception of professional activity. Indeed 30.2% of patients with a family history of affective disorders were unemployed versus 12.9% of patients without a family history of affective disorders (p = 0.02). Bipolar I patients with a family history of affective disorders were characterised by an early age at onset of the first episode (before 20 years) (48.7 versus 24.0%; p = 0.004), a high frequency of affective episodes (8.1 +/- 3.6 versus 6.0 +/- 3.5; p = 0.002) and had been more often hospitalised than patients without a family history of affective disorders (5.7 +/- 3.0 versus 4.7 +/- 3.0; p = 0.06). No significant differences were found concerning the nature of the first affective episode in bipolar I patients with or without a family history of affective disorders. Eleven women had developed their first affective episode during the puerperal period; eight of whom had a family history of affective disorders (p = 0.07). The last affective episode was significantly more severe (94.8 versus 77.8%; p = 0.003) and more often associated with psychotic features (55.3 versus 35.2%; p = 0.02) in patients with a family history of affective disorders. After multiple regression, the high frequency of affective episodes and the severity of last episode were more related with a family history of affective disorders. CONCLUSION: The results of our study provide evidence of familiality for some clinical characteristics which can be useful as phenotypic measures in future molecular genetic studies.

[Oxidative stress involvement in schizophrenia pathophysiology: a review]. / Implication du stress oxydant dans la physiopathologie de la schizophrénie: revue de la littérature.

BACKGROUND: Schizophrenia is a devastating psychiatric disorder with a broad range of behavioural and biologic manifestations. There are several clinical characteristics of the illness that have been consistently associated with poor premorbid adjustment, long duration of psychosis prior to treatment and prominent negative symptoms. The etiopathogenic mechanisms of lack of insight in patients with schizophrenia are to date unknown, although several hypotheses have been suggested. A point of convergence for the theoretical models occurs with regard to the neuronal membrane. Neuronal membrane contains a high proportion of polyunsaturated fatty acid and is the site for oxidative stress. Oxidative stress is a state when there is unbalance between the generation of reactive oxygen species and antioxidant defence capacity of the body. It is closely associated with a number of diseases including Parkinson's disease, Alzheimer-type dementia and Huntington's chorea. Accumulating evidence points to many interrelated mechanisms that increase production of reactive oxygen or decrease antioxidant protection in schizophrenic patients. OBJECTIVES: This review aims to summarize the perturbations in antioxidant protection systems during schizophrenia, their interrelationships with the characteristic clinics and therapeutics and the implications of these observations in the pathophysiology of schizophrenia are discussed. LITERATURE FINDINGS: In schizophrenia there is evidence for deregulation of free radical metabolism, as detected by abnormal activity of critical antioxidant enzymes (superoxide dismutase, glutathione peroxidase and catalase). Many studies conclude in the decrease in the activity of key antioxidant enzymes in schizophrenia. A few studies have examined levels of non enzymatic antioxidants such as plasma antioxidant proteins (albumin, bilirubine, uric acid) and trace elements. How showed decreased levels in schizophrenic patients. Others studies have provided evidence of oxidative membrane damage by examining levels of lipid peroxidation products. Such abnormalities have been associated with certain clinical symptoms and therapeutic features. Negative symptoms have been associated with low levels of GSH-Px. Positive symptoms have been positively correlated with SOD activity. Plasma TAS was significantly lower in drug-free and haloperidol treated patients with schizophrenia. A low erythrocyte SOD activity has been found in never-treated patients, but with haloperidol treatment, SOD activity increased. DISCUSSION: These results demonstrate altered membrane dynamics and antioxidant enzyme activity in schizophrenia. Membrane dysfunction can be secondary to free a radical-mediated pathology, and may contribute to specific aspects of the schizophrenia symptomatology. Membrane defects can significantly alter a broad range of membrane functions and presumably modify behavior through multiple downstream biological effects. Phospholipid metabolism in the brain may be perturbed in schizophrenia, with reduced amounts of phosphatidylcholins and phosphatidylethanolamine in post-mortem brain tissue from schizophrenic patients, and large amounts of lipofuscin-like materiel in the oligodendrocytes. The existence of these products within cell membranes results in an unstable membrane structure, altered membrane fluidity and permeability and impaired signal transduction. Recent findings suggest that multiple neurotransmitter systems may be faulty. CNS cells are more vulnerable to the toxic effects of free radicals because they have a high rate of catecholamine oxidative metabolic activity. Neurotransmitters, like glutamate, can induce the same metabolic processes that increase free radical production and can lead to impaired dopamine-glutamate balance. These results question the role of this imbalance in the biochemical basis evoked in the etipathogenic mechanisms of schizophrenia, as well as the role of antioxidants in the therapeutic strategy and their implication in preventive and early intervention approaches in populations at risk for schizophrenia.

[Repeat suicide attempts: characteristics of repeaters versus first-time attempters admitted in the emergency of a Tunisian general hospital]. / Les récidives suicidaires: etude comparative des caractéristiques des suicidants a répétition et des primosuicidants i admis aux urgences d'un hôpital général Tunisien.

UNLABELLED: Repeat suicide attempts constitute a special problem in suicidology. It seems that the excess mortality by suicide is even higher among the suicide repeaters. The objectives of this study were to estimate repeat suicide attempts frequency among a sample of suicide attempters admitted in the University Hospital Emergency of Monastir (Tunisia), to compare their features to those of first-time attempters and to determine factors associated with repeat suicide. METHOD: A transversal survey involves a review of all patients committing suicide attempt and who are admitted in the emergency service during the second semester of 1999. Study variables included: demographic parameters, family and personal psychiatric history, axis I psychiatric disorder and circumstances of the present suicide attempt. Also, subjects were evaluated with the following scales: Montgomery and Asberg Depression Rating Scale (MADRS) and The Social Readjustment Rating Scale of Holms and Rahe. RESULT: Among the 90 suicide attempters, 42.2% (n = 38) had made at least one previous suicide attempt. More repeaters than first-time attempters were divorced or separated: 21.1% versus 5.8% (p = 0.05). Belonging to a numerous family (n > or = 4) was more frequent in the repeaters group: 73.7% versus 46.2% (p = 0.01). The two groups did not differ as to level of education but were significantly different with regard to their professional activity: 60.5% of repeaters were unemployed versus 34.6% of first-time attempters (p = 0.01). Repeaters had more loaded family psychiatric disorders: 26.3% versus 7.7% (p = 0.03). However there were practically no differences between repeaters and first-time attempters in regard of suicide in their families. Personal previous history of repeaters was characterized by frequency of psychiatric hospitalization: 50% versus 11.5% (p = 0.00005). Sexual abuse was more frequent in repeaters group but this difference was not significant. Alcohol and drug abuse were not frequent in the two groups. Concerning the actual suicide attempt, the most frequently diagnosed disorder was adjustment disorders. However depressive and psychotic disorders were significantly more frequent in the repeaters group: 34.2% versus 13.4% (p = 0.05). Repeaters had more frequently elevated scores (> 14) in MADRS: 71.1% versus 48.1% (p = 0.01), and raised intensity of stress factors lived during the six months preceding actual suicide attempt: 68.4% versus 42.3% (p = 0.04). Nevertheless we hadn't noticed any differences between the two groups regarding the methods used or the motives. CONCLUSION: Differences in the characteristics of repeaters and first-time attempters are therefore of interest when discussing future suicidal risk and should clear on preventive actions in order to face the increase of suicidal recidivism. A broad based, multidisciplinary intervention approach is recommended.

[Bipolarity correlated factors in major depression: about 155 Tunisian inpatients]. / Facteurs corrélés à la bipolarité dans les dépressions majeures: étude d'une population hospitalière tunisienne.

The distinction between the depressive troubles according to their inclusion in bipolar disorders or in recurrent depressive disorders offers an evident practical interest. In fact, the curative and mainly the preventive treatment of these troubles are different. So it is necessary to identify the predictive factors of bipolar development in case of inaugural depressive episode. In 1983, Akiskal was the first who identified those factors: pharmacological hypomania, puerperal depression, onset at early age (<25 years), presence of psychotic characteristics, hypersomnia and psychomotor inhibition. Through this study, the authors try to compare the epidemiological, clinical and evolution characteristics of major depression in bipolar disorders to recurrent depressive disorders in order to indicate the correlated factors with bipolarity. It is a retrospective and comparative study based on about 155 inpatients for major depressive episode during the period between January 1994 and December 1998. These patients were divided into two groups according the DSM IV criteria: bipolar group (96 patients) and recurrent depressive group (59 patients). Both groups were compared according to socio-demographic data, life events in childhood, personal and family history, clinical and evolution characteristics of the index depressive episode. The predictive factors proposed by Akiskal were systematically examined. It was found out that the following factors were correlated with bipolarity: high rate of separation and divorce (17.7% versus 5.1%; p=0.02), family history of psychiatric disorders (56.3% versus 35.6%; p=0.012) especially bipolar ones (29.2% versus 3.4%; p=0,00008), onset at early age (mean age of onset: 24.8 8.2 years versus 34.1 12.6 years; p=0.000004), number of affective episode significantly more frequent (mean 3.6 versus 2.5; p=0.03), sudden onset of depressive episode (44.8% versus 15.9%; p=0.0003) and presence of psychotic characteristics (69.8% versus 16.7%; p=0.0001) catatonic characteristics (37.3% versus 20.3%; p=0.03), hypersomnia (51% versus 20.3%; p=0.03) and psychomotor inhibition (83.3% versus 42.4%; p=0.00007). Negatively correlated factors of bipolar depression were: somatic comorbidity such as diabetes, hypertension and rhumatismal diseases (12.5% versus 28.8%; p=0.012) and association with dysthymic disorders (2.2% versus 12.1%; p=0.029). No correlation was found between bipolarity and life events in childhood, seasonal character, alcoholic dependence and suicide attempt. Concerning the validity of predictive factors of bipolarity proposed by Akiskal, we found: history of bipolar disorders (Sensibility: 29.2%, specificity: 96.6%, Positive Predictive Value (PPV): 93%), hypersomnia (Sensibility: 51%, specificity: 80%, PPV: 80%), onset before the age of 25 years (Sensibility: 62.5%, specificity: 70%, PPV: 77%), psychomotor inhibition (Sensibility: 83.3%, specificity 58%, PPV: 76%), and psychotic characteristics (Sensibility: 69.8%, specificity: 62.7%, PPV: 75%). In spite of methodological differences, our results tallied with the other studies. We focus on the importance of the bipolar family history criterion, which has the highest PPV, and the limits of psychotic characteristics criterion which has the lowest PPV. This may be explained by the frequency of these characteristics of affective disorders in our cultural context. The association of the hypersomnia and psychomotor inhibition in one criterion in order to increase their diagnostic power. Our study helps us to identify the factors that would predict the bipolar evolution of a depressive episode allowing the use of specific treatment and ensuring the improvement of prognostic.

[Glutaminergic hypothesis of schizophrenia: clinical research studies with ketamine]. / Hypothèse glutamatergique de la schizophrénie: apports des recherches cliniques sur la kétamine.

Several lines of evidence suggest that the glutamatergic N-methyl-D-aspartate (NMDA) receptor is involved in schizophrenia pathophysiology. Post-mortem studies have revealed a lower density of glutamatergic receptors in patients with schizophrenia. Other studies of cerebrospinal fluid reported lower levels of glutamate in patients with schizophrenia in healthy comparison subjects. The most compelling evidence is provided by the psychomimetic effects of the NMDA antagonists phencyclidine and ketamine. Recently, much interest has been given to the study related to the role of NMDA receptor in pathophysiology of schizophrenia by administration of sub-anesthetic doses of ketamine. A phencyclidine hydrochloride derivate, ketamine, is a dissociative anesthetic and a non competitive antagonist of the NMDA receptor. In healthy subjects, ketamine produces: 1) positive symptoms of psychosis, such as illusions, thought disorder and delusions; 2) negative symptoms similar to those associated with schizophrenia including blunted emotional responses, emotional detachment, and psychomotor retardation; 3) cognitive impairments, in particular impairments on tests of frontal cortical function including increased distractibility, reduced verbal fluency and poorer performance on the Wisconsin Card Sorting Test. During smooth pursuit eye tracking, ketamine induces nystagmus as well as abnormalities which are among the characteristics of schizophrenia. In patients with schizophrenia, the administration of ketamine produces an activation of their psychotic symptoms, which have striking similarities to symptoms of their usual psychotic episodes. Ketamine effects on memory and other cognitive functions in schizophrenic patients are controversial. The psychomimetic effects of ketamine are transitional, reversible and influenced by time, dose and administration conditions. Susceptibility to the psychotomimetic effects of ketamine is minimal or absent in children and becomes maximal in early adulthood. The similarity between ketamine effects and endogenous psychoses created interest in the capacity of antipsychotic medications to block ketamine effects. Haloperidol failed to block this ketamine-induced psychomimetic effects in healthy subjects and in schizophrenic patients. However, clozapine, the prototype of atypical antipsychotic agents significantly reduced the ketamine-induced increase in positive symptoms in schizophrenic patients. Recently, lamotrigine significantly decreased ketamine-induced positive and negative symptoms in healthy subjects. Brain regions responsible for NMDA-mediated psychosis have not been established. Using positron emission tomography and [18F] fluorodeoxyglucose, the sub-anesthetic ketamine administration produces bilateral increases in metabolic activity in the prefrontal cortex. In a [15O] H2O positron emission tomography study, ketamine selectively increases cerebral blood flow in the anterior cingulate cortex and reduces cerebral blood flow in the hippocampus and primary visual cortex. The mechanism of neuropsychiatric effects of sub-anesthetic ketamine is not clear. A dysfunction in glutamate-dopaminergic interactions has been suggested as a mechanism for these effects of ketamine. Ketamine has been reported to primarily block NMDA receptor complex giving support to a glutamate deficiency hypothesis in schizophrenia. In addition, ketamine caused increases in cortical and striatal synaptic dopamine concentrations. The effects of NMDA receptor antagonist administration are argued to support a neurobiological hypothesis of schizophrenia, which includes pathophysiology within several neurotransmitter systems, manifested in behavioral pathology. Pharmacological modulation of the effects of NMDA receptor antagonists, such as ketamine, may lead to development of novel therapeutic agents for psychiatric illnesses such as schizophrenia.

[Pharmacological modulation of the effects induced by ketamine at subanesthetic doses]. / Modulation pharmacologique des effects induits par la kétamine à des doses subanesthésiques.

The similarity between ketamine effects and endogenous psychoses has created interest in the capacity of antipsychotic medications to block ketamine effects. In healthy subjects, a sub-anaesthetic single dose of lorazepam, typical neuroleptics, such as haloperidol, and atypical neuroleptics, such as clozapine and olanzapine, failed to block ketamine-induced positive and negative symptoms resembling schizophrenia. However, haloperidol is able to decrease ketamine-induced impairment in executive cognitive functions. Recently, lamotrigine reduced ketamine-induced psychotic symptoms, perceptual alterations, and cognitive impairments. In schizophrenic subjects, single doses of olanzapine do not decrease the effects of ketamine. However, long term treatment with clozapine has been reported to decrease ketamine-induced positive symptoms. Pharmacological modulation of the effects of NMDA receptor antagonists, such as ketamine, may lead to development of novel therapeutic agents for psychiatric illnesses such as schizophrenia.

[Acute nuptial psychosis: apropos of 16 cases]. / Les psychoses aiguës nuptiales: à propos de 16 observations.

The marriage, an over-invested social event in our Maghrebin cultural context, can, in certain cases, generate major psychiatric disorders especially of psychotic types. The aim of our study is to describe the clinical specifications of these psychotic disorders and to discuss the surroundings and individuals factors incriminated in their genesis. Our retrospective study concerns sixteen patients suffering from acute psychotic disorders precipitated by marriage. Male subjects represented 75% of cases with an average age of 26.8 years. 62.5% of them have no psychiatric background. The disorders first appeared after the marriage in 75% of cases, often during the first week. 68% of cases have delirious syndrome. Schizophreniform and brief psychotic disorders were often reported. The importance of the cultural factors was particularly prominent in the starting of these disorders.