Complications obstétricales dans la schizophrénie : étude comparative en population tunisienne

The neurodevelopmental hypothesis in schizophrenia argues that this disorder may be a result of abnormal brain development due to genetic risk and or to environmental injury such as those due to obstetric complications. Very few studies from emerging countries have been published concerning obstetric complications in schizophrenia. However, meteorological, demographic and health factors in most of these countries are different from those in Western countries, and studies in this field may bring more findings. Our objectives were to compare the frequency of obstetric complications in a group of schizophrenic patients compared to two other groups: a group of first-degree relatives and a healthy control group, and to search for the relationships between these complications and the epidemiological and clinical features of schizophrenic patients. The study is a retrospective case-controlled one: a schizophrenic patient group (N = 55, 43 males and 12 females, median age = 30 years) was compared to a group of non-affected first degree relatives (N = 40, 31 males and 9 females, median age = 29 years) and to healthy controls without familial psychiatric history (N = 38, 25 males and 13 females, median age = 29 years), all matched according to age and sex. Obstetric complications were collected at home from the biological mothers at the time of a visit using the McNeil-Sjostrom questionnaire. Schizophrenic patients were clinically assessed using the Positive and Negative Symptoms (PANSS), the General Assessment of Functioning (GAF) and the Clinical Global Impressions (CGI). Obstetric complications frequency was significantly higher in schizophrenic patients: 67,3 versus 20,0% in their non affected relatives and 28,9% in the healthy controls (P < 0,001). The mean total score of obstetric complications was significantly higher in the schizophrenic group: 1,52 ± 1,47 versus 0,8 ± 1,77 in the non affected relatives and 0,5 ± 0,97 in the healthy controls (P < 0,001). In the schizophrenic patients, obstetric complications were more frequent during delivery period (50,9%) and neonatal period (45,5 %). More particularly in pre-term births (21,8%), low birth weight and fetal distress (18,2%) and premature rupture of the membranes (16,4%). A statistical relationship was established between obstetric complications frequency, autumn-wintry birth season, low school level and negative symptoms in the PANSS. However, no significant correlation was found between obstetric complications frequency, family psychiatric history and age of onset of schizophrenia. Through an investigation involving mental recall, our results proved a higher frequency of obstetric complications in schizophrenic patients. Our results support the role of obstetric complications in the etio-pathology of schizophrenia, in interaction with other environmental or genetic factors. This association favors the neuro-developmental hypothesis in schizophrenia. Further studies assessing influence of weather, specific infectious agents, and demographic factors could also be relevant.     

Les anomalies morphologiques mineures dans la schizophrénie : étude d'une population tunisienne

Minor physical anomalies are slight dysmorphic features representing subtle alterations in the development of various bodily structures in the mouth, eye, ear, head, hand, and feet areas. The aim of this study was to assess the frequency and the type of minor physical anomalies in patients with schizophrenia in a Tunisian population. One hundred adult patients (67 men, 33 women, mean age : 38 years (S.D = 10.6), mean age of onset : 24.1 years (S.D = 6.5), educational level : 8 years (S.D = 4.7)) and 143 comparison subjects (95 men, 48 women); mean age : 42.8 years (S.D = 16.6), educational level: 5.7 years (S.D = 4.7) were assessed by using Gourion's scale which consists of 41 minor physical anomalies. The total score in patients with schizophrenia (mean: 1.7, S.D = 1.34) was significantly high than in healthy subjects (mean : 1.2, S.D = 1.06). The cut-off score that optimally discriminated the patients from comparison subjects (maximizing sensitivity and specificity for schizophrenia) was two or more. A score of two or more classified 51% of the patients and 64.3% of the comparison subjects. A higher rate of minor physical anomalies was more specific and rare. Patients showed a higher rate for 20 anomalies, the differences reaching statistical significance for six of them : asymmetric ears (Patients: 5%, Controls: 0%), curved fifth finger (Patients: 7%, Controls: 0.7%), syndactily (Patients: 5%, Controls: 0%), gap between first and second toe (Patients: 12%, Controls : 2.1%), overlapping toes (Patients: 8%, Controls: 1.4%) and asymmetric feet (Patients: 7%, Controls: 0.7%). Nine anomalies were less frequent in patients and only one reached statistical significance : palate anomalies (Patients: 7%, Controls: 17.5%). Twelve anomalies were absent in both groups (large nose basis, facial asymmetry, ptosis, coloboma, low seated ears, furrowed tongue, cleft lip, abnormal palm creases, overlapping fingers, small fingernails, asymmetric hands and hyper-convex toenails). The total score was significantly correlated with the age of onset (R = -0.21, P = 0.03) but not with illness severity (CGI score and number of hospital admissions / duration of illness). Reviewing results of similar studies in other populations, Tunisian patients with schizophrenia seem to have fewer minor physical anomalies. Only three significant frequent anomalies were concordant with results of one another study (curved fifth finger, syndactily and gap between 1^st and 2^nd toe). This large heterogeneity might be explained by ethnic variability. More studies are needed.     

Admixture analysis of age at onset in schizophrenia: evidence of three subgroups in a first-episode sample

Objective

The objective was to assess the presence of different subgroups, via age-at-onset (AAO) analysis, in a schizophrenia population consecutively recruited through an Early Psychosis Service in London, Canada.

Method

Admixture analysis was applied in order to identify a model of separate normal distribution of AAO characterized by different means, variances and population proportions to allow for evaluation of different subgroups in a sample of 187 unrelated patients with a Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, diagnosis of schizophrenia.

Results

The best-fitting model suggested three subgroups with means and standard deviations of 16.8±1.9, 22.3±2.1 and 32.7±5.9 years comprising 41%, 30% and 29% of the schizophrenia sample, respectively. These three subgroups were categorized as early, intermediate and late onset with cutoffs determined by admixture analysis to be 19 and 26 years of age, respectively. In our investigation, the definition of early-onset schizophrenia is the main outcome. We considered the clinical variables mainly related to the heritability and neurobiology of schizophrenia. Single status was strongly associated with early onset (P< .001). The male gender (P= .023), as well as a history of drug abuse (P= .004), was significantly associated with early onset. Interestingly, lower academic achievement was also associated with early-onset schizophrenia (P< .001).

Conclusion

Overall, our study showed that a typical early-onset schizophrenia patient is more likely to be a single male, with a history of drug abuse and birth complications, and lower academic achievement as compared to the late-onset subgroup.     

La myasthénie associée aux thymomes : particularités cliniques et résultats chirurgicaux

Objective

The aim of this study was to compare the characteristics of myasthenic patients with and without thymoma, and the results of thymectomy in both types of patients.

Material and methods

A retrospective study was conducted among 66 patients who underwent thymectomy for myasthenia gravis in our department over a 10-year period (2000–2010). The surgical approach was sternotomy or anterolateral thoracotomy. Patients were divided into two groups according to the presence of thymoma: with (T-MG) and without (NT-MG) thymoma. Complete stable remission (CSR) was the primary endpoint.

Results

Median age was 35.09 ± 9.89 years. The NT-MG group had 38 patients (57.57%) and the T-MG group 28 patients (42.43%). There was no difference between the two groups regarding the surgical approach (P = 0.52). T-MG patients were older (40.54 ± 15.16 vs. 31.37 ± 9.46) (P = 0.008) and predominantly male. There were more generalized forms (P = 0.01) and more bulbar involvement (P = 0.02) in the T-MG group. The rate of CSR at 5 years was 7% and 17% in the T-MG and NT-MG patients respectively (P = 0.70). At 10 years, it was 36% and 94.73% respectively (P = 0.03).

Conclusion

Thymomatous myasthenia gravis is characterized by the severity of its clinical features. Remission rate at 10 years was significantly lower in the myasthenia with thymoma group.     

Déficits des fonctions exécutives dans la schizophrénie selon les dimensions positive, négative et de désorganisation

The aim of this study was to examine whether executive deficits underlie positive, negative and disorganisation of schizophrenia. The sample comprised 34 patients (30 males, 4 females) diagnosed with DSM-IV criteria (mean age = 35 ± 9.5 years; mean duration of illness since first psychotic symptoms = 10.2 ± 7 years; mean years of education = 11.7 ± 2.6). Evaluation of patients was performed after achieved sufficient remission (clinically stable for 4 weeks at least, no depressive symptoms at moment of cognitive testing and no medication change during the three last weeks). Symptom dimensions were evaluated using items drawn from the Positive And Negative Symptoms Scale (PANSS). The Negative factor comprised N1 (blunted affect), N2 (emotional withdrawal), N3 (poor contact), N4 (passive, apathetic), N6 (lack of spontaneity), G7 (stereotyped thinking) and G16 (active social avoidance). The Positive factor comprised P1 (delusions), P3 (hallucinatory behaviour), P5 (grandiosity), P6 (suspiciousness) and G9 (unusual thought content). The Disorganisation factor comprised P2 (conceptual disorganisation), N5 (difficulty in abstract thinking), G10 (disorientation) and G11 (poor attention). The mean total PANSS score was 63.3 ± 16 (mean of positive score = 14.3 ± 4.7; mean of negative score = 18.1 ± 6.3; mean of general score = 30.9 ± 8.5). Executive functions were examined through the Wisconsin Card Sorting Test (WCST), the Hayling Test (Tunisian version) and two semantic verbal fluency tasks (simple with one category “animals” and alternating with two categories “fruits and clothes”). Partial correlations between syndrome scores and cognitive scores were examined while holding the effects of other symptoms, age and education level constant. Severity of disorganisation symptoms correlated with high number of perseverative errors (r = 0.47, P < 0.05) and total errors in the WCST (r = 0.37, P < 0.05) and with reduced score of alternating semantic verbal fluency (r = -0.39, P < 0.05). Severity of both negative and positive dimensions uncorrelated with performance of any of the executive tasks. Also, scores of the Hayling Test (time part B minus time part A; errors part B) and semantic simple verbal fluency (total of correct words) were uncorrelated with symptoms. The present study provides evidence that disorganisation dimension of the PANSS correlates specifically with impaired cognitive flexibility as reflected by high number of perseveration in the WCST and reduced set-shifting in semantic alternating verbal fluency.     

Emotion processing and theory of mind in schizophrenia patients and their unaffected first-degree relatives

Previous studies have suggested that social cognition is affected in individuals with schizophrenia. The purpose of this study was to explore to what extent social cognition deficits are shared by unaffected first-degree relatives, and the nature of the relationship between performance in different paradigms of social cognition. 20 Schizophrenia patients (7 females, 31 ± 10 years), 20 healthy age- and gender-matched individuals, 20 unaffected first-degree relatives of the schizophrenia patients (11 females, 50 ± 20 years), and 20 healthy individuals matched for age and gender were recruited. Patients showed deficits in the detection of social Faux Pas (0.80 ± 0.17 vs. controls: 0.94 ± 0.09, p = 0.025) and the correct identification of Theory of Mind stories (0.71 ± 0.13 vs. controls: 0.82 ± 0.12, p = 0.038). Relatives performed poorly in the Faces Test (0.83 ± 0.14 vs. controls: 0.9 ± 0.08, p = 0.048), the Reading the Mind in the Eyes Test (0.59 ± 0.17 vs. controls: 0.71 ± 0.14, p = 0.046) and the detection of social Faux Pas (0.8 ± 0.2 vs. controls: 0.93 ± 0.09, p = 0.024). Abnormalities were independent of age, years of education, and general cognitive performance in patients and their relatives. Performance in an Emotion Processing task (Faces Test) was correlated with performance in theory of mind tests in healthy individuals and relatives of patients with schizophrenia only. These results suggest that schizophrenia patients and their unaffected first-degree relatives display similar but nonidentical patterns of social cognition processing.     

De la non-expression à la surexpression des émotions ou comment l’expérience émotionnelle repose la question des liens entre sexe, alexithymie et répression

Objectives

Alexithymia, considered as a disorder of affect regulation, is well known for its consequences on the vulnerability to negative emotions, but nevertheless it raises the question of the repressive dimension according to Myers’ (1995) and Newton and Contrada’s (1994) researches. If, under certain conditions, alexithymia refers to this dimension we should observed traces of this repressive behaviour on emotional distress. We thus studied the influence of alexithymia scores on trait anxiety, state anxiety and depression, and this relatively to the gender of the participants.

Methodology

We first compared the mean scores of distress of our three groups of subjects (low alexithymia, N = 32; moderate alexithymia, N = 62, high alexithymia, N = 33) with the norms of the general population. Secondly, we studied the consequences of alexithymia intensity on depressive symptoms, trait and state anxiety, with regard to the gender differences. We used 1) the State-Trait Anxiety Inventory (Spielberger) to assess dispositional and acute anxiety, 2) the Center for Epidemiological Scale for Depression (Radloff) to evaluate depressive symptomatology and 3) the Toronto Alexithymia Scale (Bagby) for the alexithymia construct.

Results

In the lower alexithymia group, the total mean scores of depression for men or women (men: 8.06 ± 7.06; women: 8.88 ± 6.84) were significantly lower than those in the general population (men: 12.73 ± 3.02; women: 13.97 ± 3.62). We obtained the same pattern of consequences of a low alexithymia with regard to trait anxiety (men: 32.73 ± 10.20 versus 41.86 ± 9.48; women: 37.17 ± 8.48 versus 45.09 ± 11.11). Finally, there was no difference between the lower alexithymia group mean scores and the general population references, regardless of gender. In addition, in our group of women, the higher the alexithymia mean scores, the more important were the depression (F(2,68) = 21.13, P ≤ 0.000), trait anxiety (F(2,68) = 12.51, P ≤ 0.000) and state anxiety (F(2,68) = 6.72, P ≤ 0.002) mean scores. The male participants did not show a particular vulnerability to the alexithymia intensity, except for trait anxiety in the moderate condition (t(43) = -2.30, P ≤ 0.026).

Conclusion

Our results support the reality of the emotional repression in the condition of lower alexithymia and raise the question of the links between alexithymia and gender. Indeed, emotional experience follows different and surprising ways, inviting us to think about the relevance of a differentiation of the type of alexithymia according to whether one is a man or a woman.     

Decreased serum BDNF levels in chronic institutionalized schizophrenia on long-term treatment with typical and atypical antipsychotics

Accumulating evidence showed that brain-derived neurotrophic factor (BDNF) may be involved in the pathophysiology of schizophrenia. Decreased BDNF levels have been found in the serum of schizophrenic patients with mixed results. In the present study, we assessed serum BDNF levels in a large group of 364 schizophrenic patients (157 on clozapine, 89 on risperidone and 118 on typical antipsychotics), compared to 323 healthy control subjects matched for age and gender. The schizophrenia symptomatology was assessed by the Positive and Negative Syndrome Scale (PANSS), and serum BDNF levels were measured by sandwich ELISA. The results showed that BDNF levels were significantly lower in chronic patients with schizophrenia than in healthy control subjects (9.9 ± 2.0 ng/ml vs.11.9 ± 2.3 ng/ml, p < 0.0001). Lower BDNF levels were observed in patients treated with risperidone (9.3 ± 2.3 ng/ml) compared to those with clozapine (10.2 ± 2.0 ng/ml, p < 0.001) and typical antipsychotics (10.0 ± 2.1 ng/ml, p < 0.01). Furthermore, a stepwise multiple regression analysis identified types of antipsychotic drugs (beta = − 0.37, t = − 3.15, p = 0.001) and BDNF levels (beta = − 0.26, t = − 2.51, p = 0.014) as the influencing factor for the positive symptom subscore of PANSS. In addition, there was a sex difference in BDNF levels in patients with schizophrenia (9.7 ± 1.9 ng/ml for males vs.10.4 ± 2.1 ng/ml for female, p < 0.005), but not in normal controls. Our findings indicated decreased BDNF serum levels in chronic patients with schizophrenia, which may be related to clinical phenotypes, including gender, antipsychotic treatment and the severity of psychotic symptoms.     

Évolution clinique de la dépression post-accident vasculaire cérébral à Kinshasa

Objectives

To describe the evolution of the clinical profile of post-stroke depression over a period of one year and to determine factors associated with changes in post-stroke depression.

Methods

Prospective cohort study with a follow-up of 1 year including 30 consecutive eligible patients. The severity of depression was assessed with the patient health questionnaire (PHQ9).

Results

The mean age was 55.87 ± 12.67 years. Seventy percent of patients were men. The two assessments for neurological status, perceived health status and test results of attention were not statistically different. The rate of depressive symptoms was 26.67% in 2011 and 20% in 2012. Disability and apathy were significantly improved. The average for disability increased from 2.77 ± 1.19 to 2.46 ± 2.19 (P = 0.002). From 66.7% in 2011, the proportion of patients able to walk without assistance rose to 93.3% in 2012 (P = 0.03). In addition, the proportion of patients apathetic decreased from 43.3% to 13.3% (P = 0.01). Greater age, female sex, sleep disorders and post-stroke apathy remained associated with DPAVC between the two assessments, with an increase in the strength of the association for apathy.

Conclusions

The frequency of post-stroke depression is high and remains stable over time. Disability is the clinical feature that evolved more favorably. The association with apathy, present at the beginning, of the study was strengthened one year later.     

Correlates between neurological soft signs and saccadic parameters in schizophrenia

Objective

Neurological Soft Signs (NSS) and impairments in oculomotor saccadic paradigms are both frequent in patients with schizophrenia but their correlation has never been explored.

Methods

78 patients with DSM-IV schizophrenia (including 43 non-treated) and 41 matched healthy controls were tested for NSS, and on three saccadic tasks: prosaccades, predictive saccades and memory-guided saccades) using infrared oculometry. We analyzed correlations between NSS scores and latencies in all three tasks, rate of errors in memory-guided saccades, and rate of anticipated predictive saccades.

Results

No correlations were found in healthy controls. In the patient group, the NSS total and motor coordination scores were positively correlated with three saccadic variables: the latency of prosaccades (r = 0.36, p < 0.01 and r = 0.36, p < 0.01 respectively), of memory-guided saccades (r = 0.35, p < 0.01 and r = 0.32, p < 0.05 respectively) and, negative correlations were found, with the rate of anticipated predictive saccades (r = − 0.33, p < 0.01; r = − 0.35, p < 0.01 respectively). NSS total, motor coordination and sensory integration scores were correlated to the latency of non-anticipated predictive saccades (r = 0.34, p < 0.01; r = 0.24, p < 0.05 and r = 0.40, p < 0.001 respectively). The NSS total, motor integration and sensory integration scores were correlated with the rate of errors in memory-guided saccades (r = 0.38, p < 0.01; r = 0.37, p < 0.01 and r = 0.34, p < 0.01 respectively).

Conclusions

These results support a common pathological mechanism with partial overlapping neural substrates between NSS and saccades in schizophrenia.     

Estimation of sleep disturbances using wrist actigraphy in patients with postural tachycardia syndrome

Study objectives

Patients with postural tachycardia syndrome (POTS) commonly complain of fatigue, unrefreshing sleep, daytime sleepiness and diminished quality of life. The study objective was to assess sleep quality in POTS patients using wrist actigraphy.

Design

Prospective study with control group.

Methods

Patients with POTS (n = 36) and healthy subjects (n = 36) completed a detailed sleep log and actigraphy for 7 days.

Results

Compared with healthy subjects, POTS patients have more self-reported problems including days with restless sleep (53 ± 30% vs. 21 ± 20%; P < 0.001) and tiredness (75 ± 23% vs. 39 ± 27%; P < 0.001). Using actigraphy, POTS patients have lower sleep efficiency (73 ± 13% vs. 79 ± 6%; P = 0.01). Actigraphy determined sleep onset latency (SOL) did not vary significantly in the two groups, but subjective SOL was higher in POTS patient (56 ± 66 min vs. 13 ± 9 min; P = 0.001). In POTS patients, there was a significant correlation between subjective complaints of tiredness and actigraphic sleep efficiency (Rs = − 0.36; R² = 0.15; P = 0.01), significant correlations between actigraphic SOL and upright norepinephrine levels (P = 0.040), and between wake after sleep onset and standing heart rate (P = 0.02).

Conclusions

POTS patients have more sleep-related symptoms and poor sleep efficiency. The pattern of subjective vs. objective SOL mismatch is suggestive of sleep-state misperception. High norepinephrine correlated with actigraphic SOL, and this activation of the stress system may contribute significantly to a hyperarousal state with consequent insomnia, poor mental and physical health in POTS patients.     

Higher serum clozapine level is associated with increased antiphospholipid antibodies in schizophrenia patients

Objectives

This study was to evaluate the relationship between clozapine and aPL in schizophrenia patients.

Methods

163 Participants were evaluated: 37 unmedicated schizophrenia patients, 50 clozapine-treated schizophrenia patients and 76 age- and sex-matched healthy controls. A fasting blood sample was taken for serum aPL and serum clozapine level. Serum aPL were measured by ELISA technique and HPLC method was used for the determination of serum clozapine level.

Results

The unmedicated schizophrenia patients showed higher IgG aCL level [mean ± SD: 1.51 ± 0.81 and 1.25 ± 0.13 U, respectively (t = 2.77, df=111, p<0.01)] and IgM aCL level [mean±SD: 1.53 ± 0.54. and 1.33 ± 0.15 U, respectively (t = −2.98, df = 111, p < 0.01)] compared with the healthy controls. The comparison of the clozapine-treated schizophrenia patients and the healthy controls showed significant difference in IgG aCL level [mean ± SD: 1.74 ± 0.90 and 1.25 ± 0.13 U, respectively (t = −4.77, df = 124, p < 0.01)] and IgM aCL level [mean ± SD: 1.62 ± 0.83 and1.33 ± 0.15 U, respectively (t = −4.35, df = 124, p < 0.01)]. In clozapine-treated schizophrenia patients, the results of Pearson correlation coefficients showed that there was a significant positive relationship between serum IgM aCL and serum clozapine level (r = 0.461, p < 0.01), and serum IgG aCL were significantly correlated with serum IgM aCL (r = 0.279, p < 0.05). Stepwise multiple regression analysis was performed with various characteristics, such as duration of medication, daily dose and serum clozapine level as candidate factors for serum aCL (IgG and IgM isotypes) in clozapine-treated schizophrenia patients. Only serum clozapine level was able to enter into the regression model of IgM aCL (Model R² = 0.212, p < 0.05).

Conclusions

A higher serum clozapine level is associated with an increased aPL in schizophrenia patients.     

Schizophrénie et immigration : influence des facteurs psychosociaux

Introduction

Several studies showed that the prevalence of schizophrenia among immigrants is high. This prompted the authors to investigate the links between schizophrenia and immigration status.

Methodology

We conducted a retrospective study psychiatric service in Mahdia hospital over a period of 5 years and a half from January 2003 to June 2010, including patients hospitalized, diagnosed as having schizophrenia; and having immigration and living abroad experiences.

Results

These 50 male patients of average age 32 years. Forty-two patients (84%) were single. The socioeconomic conditions were low in all cases. Nine patients had familial psychological disorders. Sixteen patients (32%) had a criminal past. Immigration was illegally in 39 cases (78%). Destination countries’ were European in all cases. Duration of immigration was on average 37.3 months. Thirty-one (62%) patients reported experiences of incarceration and experiences of discrimination abroad. The clinical presentation was dominated by disorganized schizophrenia: 37 patients (74%). Eighteen patients (36%) reported drugs consumption. The psychosocial stress was according to DSM IV-TR, professional problems and problems related to social environment.

Conclusion

It seems that besides the biological and neuro-developmental schizophrenia hypotheses, there are psycho-social hypotheses: social stress. Other studies are needed to support these hypotheses.     

Insight, dépression, estime de soi et satisfaction de vie chez des personnes souffrant de schizophrénie

Recent studies on insight in schizophrenia, mainly english-speaking, have shown that denial of mental disorder (lack of insight) is connected with a less good compliancy with treatment. Consequently, therapies, which increase insight, develop currently (psychoeducation and information of patients, for instance). Nonetheless, certain studies concluded that awareness of mental disorder has a negative effect on psychological dimensions like humor, self-esteem and quality of life. So we realize a pilot-study on 20 schizophrenic subjects (DSM-IV) (15 men and five women including 13 full-time inpatients and 7 days in-patients) from 22 to 61 years (m = 41.75; σ = 11.94). The aim of the study was to measure insight (IS and Q8), depressive experience (SCL90-R and CDSS), self-esteem (SEI) and satisfaction with life (SWLS), then to calculate correlation between insight and the three other dimensions. Data analysis confirmed a strong link between insight and deterioration of self-esteem (r = −0.6922; p = 0.001) and with an increase of depressive experience (r = 0.8134; p = 0.000 with SCL90-R and r = 0.6041; p = 0.006 with CDSS). Satisfaction with life is not significantly correlated with insight (r = −0.2047; p = 0.401). Those results show that clinicians must take into account the depressive effect of therapeutic strategies aiming at an increase in insight.     

Modulation of the mineralocorticoid receptor as add-on treatment in depression: A randomized, double-blind, placebo-controlled proof-of-concept study

Preclinical and clinical studies have suggested a role of the mineralocorticoid receptor (MR) in the response to antidepressants. We tested in a proof-of-concept study whether adding fludrocortisone (an MR agonist) or spironolactone (an MR antagonist) accelerates onset of action and improves efficacy of escitalopram in patients with major depression.We included 64 in- and outpatients with major depression (Hamilton Depression Scale-17 score > 18) in a double-blind, randomized, placebo-controlled trial. Patients were randomized in a 2:2:1 fashion to fludrocortisone (0.2 mg/d, n = 24) or spironolactone (100 mg/d, n = 27) or placebo (n = 13) for the first 3 weeks during a 5-week treatment with escitalopram.No differences in mean HAMD change scores and in time to response emerged between treatments. However, among the responders, patients treated with fludrocortisone responded faster (Breslow test, p = 0.05). The mean number of days to response was 16.0 ± 2.6 days vs. placebo 22.2 ± 2.0 vs. spironolactone 22.6 ± 2.3 (F = 3.78, p = 0.03). In the whole group, plasma cortisol increased during spironolactone and decreased during fludrocortisone treatment (F = 2.4, p = 0.04). In patients treated with fludrocortisone, non-responders had elevated cortisol values compared to responders throughout the study period (F = 5.1, p = 0.04).Stimulation of MR with fludrocortisone as adjunct to escitalopram accelerated the response in the group of responders while no effect emerged in the sample as a whole. A larger randomized controlled trial is warranted.     

Clinical characteristics and treatment outcome of depression in patients with and without a history of emotional and physical abuse

Clinical features and treatment outcome were compared in depressed outpatients with and without a history of emotional and physical abuse (EPA), including childhood maltreatment. Patients were initially randomized to IPT or SSRI and then augmented with the second treatment if they did not remit with monotherapy. Assessments included the SCID-I, the SCID-II for DSM-IV diagnoses, the HRSD, the QIDS and the Mood Spectrum Self-Report (MOODS-SR). Seventy-eight (25%) patients reported a history of EPA; 60 (76.9%) were women. Patients with a history of EPA did not differ from those without on HRSD scores at baseline, but showed an earlier age at onset of depression and a longer duration of illness. The two groups differed on several mood spectrum factors, namely: ‘depressivemood’ (15.6 ± 4.9 vs. 13.5 ± 5.4; p < 0.004), ‘psychomotorretardation’ (11.7 ± 4.5 vs. 9.6 ± 4.7; p < 0.001), ‘drugandillness-relateddepression’ (1.3 ± 1.3 vs. 0.6 ± 1.0; p < 0.0001), and ‘neurovegetativesymptoms’ (8.3 ± 2.6 vs. 6.9 ± 2.9; p < 0.0001). Patients with EPA had also a significantly longer time to remission (89 vs. 67 days, log-rank test, p = 0.035). The need for augmentation treatment was significantly more frequent among patients with EPA than in those without. The present study suggests that patients with a history of EPA show a subtype of depression characterized by poor treatment response and more severe neurovegetative and psychomotor symptoms.     

Déficit émotionnel et intelligence machiavélique : étude des interrelations entre l'échelle d'alexithymie de Toronto (TAS-20) et l'inventaire mach-iv dans une population de 201 étudiants

The aim of the study was to explore the relationship between alexithymia and machiavellianism in a group of 201 university students. The subjects filled out the TAS-20 and the MACH-IV forms. The results showed firstly, a significant correlation between the two total scores (r = 0.35, P < 0.05), and secondly between the identification of feelings subscale of the TAS-20 and the opinions about human nature subscale of the Mach-IV (r = 0.44, P < 0.05). The results were discussed in light of the different factors (depression, dependency, psychoticism…) that could explain the relationship between the two concepts.     

The study of BDNF Val66Met polymorphism in Chinese schizophrenic patients

Accumulating evidence showed that brain-derived neurotrophic factor (BDNF) may be involved in the pathophysiology of schizophrenia. Recent studies have reported that the Val66Met polymorphism of the BDNF gene may be associated with susceptibility for schizophrenia and age of onset of this disease, with mix results. In the present study, the BDNF Val66Met gene polymorphism was examined in 387 inpatients (259 men and 128 women) meeting the DSM-IV criteria for schizophrenia and unrelated 365 healthy controls (255 men and 110 women). The schizophrenia symptomatology was assessed by the Positive and Negative Syndrome Scale (PANSS). Age of onset was defined as the age at which the psychotic symptoms first appeared. Our results showed that genotype frequency distributions and allelic frequencies did not differ between patients and controls. No interaction was found between sex and genotypes. Analysis of covariance (ANCOVA) showed a significance of the BDNF Val66Met genotypes on the age of onset (F = 3.76, p < 0.02), after adjusting sex, age and duration of illness. Furthermore, ANCOVA showed that the significance of the BDNFVal66Met genotypes on age of onset was increased comparing the Val66Met heterozygotes with the combination of Val66Val and Met66Met homozygotes (F = 5.85, p < 0.01). Our results suggest that the BDNF Val66Met polymorphism may not contribute directly to the susceptibility to schizophrenia, but to the onset of the disease. Furthermore, our results show the heterozygous effect of the BDNF Val66Met gene on the clinical variability of schizophrenia phenotype.     

Intérêt du programme éducationnel Soleduc pour la prévention des rechutes dans la schizophrénie

Informing schizophrenic patients of their disease is supposed to enhance compliance to antipsychotic treatments and hence to reduce the number of relapses. However, it is not clear whether the provision of psychoeducation changes schizophrenic patients’ behaviour. Recently, a two-year study of 220 schizophrenic patients was designed to evaluate the impact of a psychoeducational program (Soleduc^®) on the rate of relapses (new hospitalizations). This was a multicentric French clinical trial (51 centers) of phase IV, open, controlled, randomized, consisting in two parallel groups: the Soleduc group (N = 111) and the control group (N = 109). All schizophrenic patients were treated with the same antipsychotic drug (amisulpride). The Soleduc^® program contents were presented in 21 sessions, seven were programmed at the beginning of the study, seven at six months later and seven at 12 months. Patients in the control group received usual information on the disease during a period equivalent to the Soleduc^® program. The risk of relapse was significantly reduced for patients who followed at least five modules. In conclusion, attendance of at least five out of 21 program sessions was required to see a modest but significant two-year relapse prevention in schizophrenia. Other well-designed studies are required to evaluate the medical impact of patient's education programs.