Lotfi Gaha

Decreased glutathione levels and antioxidant enzyme activities in untreated and treated schizophrenic patients

There is substantial evidence found in the literature that supports the fact that the presence of oxidative stress may play an important role in the physiopathology of schizophrenia. Previous studies have reported the occurrence of impairments in the glutathione levels and the activities of the antioxidant enzymes in patients suffering from schizophrenia. However, most of these studies were performed on treated patients. The present study evaluated treated schizophrenic patients (n=52) along with neuroleptic-free or untreated schizophrenic patients (n=36) and healthy controls (n=46). The blood glutathione levels: total glutathione (GSHt), reduced glutathione (GSHr), and oxidized glutathione (GSSG) as well as the activities of the antioxidant enzymes: superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT) were measured. The psychopathology of the patients was assessed through the Clinical Global Impressions-severity (CGI-severity). The tests revealed that in comparison with the healthy controls, the schizophrenic patients showed significantly lower levels of GSHr, SOD, and CAT. Among the schizophrenic patients, the activities of the antioxidant enzymes SOD and CAT were recorded to be significantly lower in untreated patients than in the treated ones. In addition, the levels of both GSHt and GSHr were found to be inversely correlated with the obtained CGI-severity score. These results evidently suggest that a decrease in the glutathione levels and the activities of the antioxidant enzymes in patients diagnosed with schizophrenia is not related to neuroleptic treatment and could be considered as a biological indicator of the degree of severity of the symptoms of schizophrenia.

Implication du stress oxydant dans la physiopathologie de la schizophrénie: revue de la littérature.

Resume Le stress oxydant est la resultante d’un desequilibre entre la production de radicaux libres et les systemes de defenses antioxydants. Le systeme nerveux central, de par sa consommation importante en oxygene, sa surface etendue d’echange membranaire et un taux relativement bas d’enzymes antioxydantes, represente un lieu privilegie pour le stress oxydant. Ce dernier serait d’ailleurs implique dans plusieurs pathologies du systeme nerveux central, telles que la maladie d’Alzheimer, la maladie de Parkinson ou la choree de Hungtington. Dans ce travail, nous proposons d’etudier, a travers une revue de la litterature, les differentes perturbations des systemes antioxydants observees dans la schizophrenie, leurs correlations avec les caracteristiques cliniques et therapeutiques, et de discuter l’implication de ces observations dans la physiopathologie de la schizophrenie. Une baisse de l’activite des enzymes antioxydantes (super-oxyde dismutase, glutathion peroxydase, catalase), des concentrations plasmatiques des differents constituants du systeme de defense non enzymatique (albumine, bilirubine, acide urique, oligoelementsh) ainsi qu’une augmentation de la peroxydation des lipides ont ete constatees chez les patients schizophrenes. Ces perturbations sont correlees a la severite des signes negatifs de la maladie et peuvent etre influencees par le traitement neuroleptique. Ces resultats font suggerer la place de ces perturbations, comme base biochimique des anomalies du systeme nerveux central, observees dans la schizophrenie, et evoquer le role potentiel des antioxydants dans la strategie therapeutique.

Neurological soft signs in patients with schizophrenia and their unaffected siblings: frequency and correlates in two ethnic and socioeconomic distinct populations.

Recent studies have suggested that ethnicity and socioeconomic status may have an impact on the frequency and significance of neurological soft signs (NSS). However, this impact has not been adequately assessed. The objectives were to determine the NSS scores in patients with schizophrenia and their unaffected siblings and to examine the clinical and therapeutic correlates of NSS in two ethnic and socioeconomic distinct populations. Two independent replicate studies were carried out: (1) a French Caucasian sample of 69 patients with schizophrenia, 43 of their unaffected siblings and 108 control subjects; (2) a Tunisian sample of 66 patients with schizophrenia, 31 of their unaffected siblings and 60 control subjects. NSS were assessed with a multidimensional scale, previously validated in drug-naïve and treated samples of patients with schizophrenia. Both patient groups were assessed with the positive and negative syndrome scale (PANSS), the clinical global impressions (CGI) and the global assessment of functioning. NSS total scores were significantly higher in patients with schizophrenia comparatively to siblings and to controls in both studies. The two sibling groups had also higher NSS scores than controls. In addition, NSS total scores were correlated to the PANSS negative and disorganization sub-scores, to the CGI-severity of illness and to a low educational level in both studies. These studies provide a confirmation in two distinct samples of the high prevalence of NSS in patients with schizophrenia, and in their biological relatives, independently of their respective ethnic and socioeconomic origins.

Neurological soft signs and schizotypal dimensions in unaffected siblings of patients with schizophrenia

The objectives were to determine the neurological soft signs (NSS) scores in unaffected siblings of patients with schizophrenia compared with healthy controls and to examine their relationships with schizotypal dimensions. Participants comprised 31 unaffected siblings of patients with schizophrenia and 60 healthy controls matched according to age, gender and school level who were assessed by the Schizotypal Personality Questionnaire (SPQ) and the Krebs et al. NSS Scale. Higher NSS total scores and sub-scores were found in the unaffected siblings compared with the controls. The SPQ total score was significantly higher in unaffected siblings compared with control subjects. The NSS total score was positively correlated with the SPQ total score and the SPQ disorganization sub-score in unaffected siblings of patients with schizophrenia. Additionally, in unaffected siblings, motor coordination and integration abnormalities were positively correlated with the SPQ total score and the cognitive-perceptual sub-score. Motor integration abnormalities were also correlated with the SPQ disorganization sub-score. These results reveal that NSS, especially motor signs, are associated with some schizotypal dimensions in siblings of patients with schizophrenia, suggesting the value of using both assessments to study high risk populations.

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.

Hyperhomocysteinemia in Tunisian bipolar I patients

Aims:  The aim of the present study was to investigate hyperhomocysteinemia in Tunisian bipolar I patients according to 5,10‐methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism.

Abnormalities of auditory event-related potentials in students with high scores on the Schizotypal Personality Questionnaire

Some auditory event-related potential (ERP) abnormalities characterize both patients with schizophrenia and subjects with schizotypal personality disorder. It was therefore hypothesized that subjects from the community with schizotypal traits might also present ERP abnormalities. In this study, we compared auditory ERP latencies and amplitudes in 13 subjects with high (H-SPQ) and 12 subjects with low (L-SPQ) scores on the Schizotypal Personality Questionnaire (SPQ), selected from 198 Tunisian students. Auditory ERPs were recorded at Fz, Cz, and Pz, with a standard oddball paradigm. Smaller P300 amplitudes and delayed P300 latencies were found in H-SPQ compared with L-SPQ participants. Confirming previous reports, our results suggest that reduced P300 amplitudes and delayed P300 latencies may be considered as vulnerability markers of the schizophrenia spectrum in nonclinical subjects from the community.

Lower paraoxonase 1 activity in Tunisian bipolar I patients.

BackgroundThe purpose of this study was to investigate the variations of paraoxonase activity and lipid profile in bipolar I patients, and the association of this activity with the sociodemographic, clinical and therapeutic characteristics of this population.Patients and methodsOur study included 66 patients with bipolar I disorder and 64 controls aged 37.9 ± 12.6 and 36.3 ± 18.2 years, respectively. Paraoxonase activity was determined by kinetic methods; high-density lipoprotein cholesterol (c-HDL), low-density lipoprotein cholesterol (c-LDL), triglycerides and total cholesterol were determined by enzymatic methods; apolipoprotein (Apo)A1, ApoB and lipoprotein (a) (Lp(a)) were determined by immunoturbidimetry using Konelab 30 equipment (Thermo Scientific).ResultsCompared with controls, patients had a significantly lower paraoxonase activity and ApoA1 level, and significantly higher total cholesterol, c-LDL and Lp(a) level and ApoB/ApoA1 ratio. Furthermore, paraoxonase activity was significantly correlated with c-HDL values (r = 0.5612; P < 0.001). The lowest paraoxonase activity was noted in relation to age and body mass index (BMI). Moreover, it was associated with gender but not with smoking and alcohol consumption status. In patients, there was no significant change in paraoxonase activity in relation to illness episodes, whereas the lowest values of this activity were seen in manic patients. In contrast, paraoxonase activity was significantly associated with treatment. Indeed, patients taking lithium had the lowest levels.ConclusionsBipolar patients had a significant decrease in paraoxonase activity and perturbations in their lipid profile that contribute to increased risk of cardiovascular diseases. Decrease in this activity was significantly associated with treatment with lithium but not with sociodemographic and clinical characteristics. Therefore, such patients require specific care, particularly with regard to their lipid profile.

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 patients 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.

Neurological soft signs in euthymic bipolar I patients: A comparative study with healthy siblings and controls

Neurological Soft Signs (NSS) are endophenotypic markers widely studied in schizophrenia and remain poorly evaluated in bipolar disorder. The aims of this paper were to determine the prevalence and scores of NSS in bipolar I patients, compared to healthy siblings and controls and to explore correlations with socio-demographic and clinical features of patients. This was a case-control study comparing 92 euthymic bipolar I patients, 44 of their healthy siblings and 60 control subjects. The neurological assessment was performed through the NSS scale validated by Krebs et al. (2000). Bipolar I patients were also assessed with the Bech-Rafaelsen Mania Scale (MAS), the Hamilton Depression Rating Scale (HDRS) and the Global Assessment of Functioning (GAF). The raters were not blinded to groups. The prevalence and the total score of NSS were significantly higher in bipolar I patients compared to their healthy siblings and controls. The sibling group had significantly higher NSS prevalence and total score than controls. No correlation was found between NSS total score and socio-demographic and clinical features of patients, except a negative correlation with the school level and the GAF score. In conclusion, bipolar I patients have motor and sensory signs, which are unrelated to their clinical features.