Effects of aripiprazole, risperidone, and olanzapine on 5-HT1A receptors in patients with schizophrenia.

To investigate the impact of various antipsychotic drugs on the 5-HT1A serotoninergic system, we performed a [F]4-(2-methoxyphenyl)-1-[2-(N-2-pirydynyl)-p-luorobenzamido]-ethyl-piperazine PET study in 19 schizophrenic patients treated with either aripiprazole, which has a partial agonist activity at 5-HT1A receptors, or second-generation antipsychotics (SGA) (olanzapine or risperidone), which do not demonstrate such property. We used a simplified reference tissue model to generate parametric images of [F]MPPF-binding potential (BPND). A significant reduction of [F]MPPF BPND was found in treated schizophrenic patients compared to age- and sex-matched healthy subjects. These modifications were mainly localized in the frontal and orbitofrontal cortex and may reflect either the pathophysiology of schizophrenia or medication effects. The schizophrenic patients treated with aripiprazole showed a reduction of global [F]MPPF BPND compared with healthy subjects and schizophrenic patients with SGA treatment. In addition, compared with matched controls, the reduction of regional [F]MPPF BPND was more marked in the schizophrenic patients treated with aripiprazole compared with those receiving SGA treatment, possibly reflecting the partial agonist of aripiprazole activity at 5-HT1A receptors.

Summer birth and deficit schizophrenia in Tunisia.

Summer birth has been associated with the deficit Schizophrenia syndrome, while DSM-IV schizophrenia is associated with winter birth. We confirm these monthly differences in a Tunisian sample of patients with schizophrenia, with a summer birth peak (n=34 deficit patients) and an expected winter birth peak (n=46 non-deficit patients).

Visual-perceptual abilities in healthy controls, depressed patients, and schizophrenia patients.

Previous studies have suggested a right hemineglect in schizophrenia, however few assessed possible visual-perceptual implication in this lateralized anomaly. A manual line bisection without (i.e., lines presented on their own) or with a local cueing paradigm (i.e., a number placed at one or both ends of the line) and the Motor-free Visual Perceptual Test-Vertical format (MVPT-V) were used to assess the visual-perceptual abilities of healthy controls, schizophrenia and depressed patients. Whereas healthy controls and depressed patients showed a non-significant leftward bias in manual line bisection, schizophrenia patients bisected significantly to the left of the true centre of the line. Interestingly, the pattern of performances in response to the local cueing paradigm was similar in depressed and schizophrenia patients such that both groups demonstrated a significant change in their bisection performance only in response to a cue placed at the right extremity of the line (control performance was modified by cues at either end of the line). Finally, in the MVPT-V, schizophrenia patients were impaired relative to the other two groups, especially in the spatial working memory and visual closure categories. These results suggest that: 1/a deficit towards the right hemifield, consistent with a mild form of right hemineglect, can be observed in schizophrenia; 2/lateralized anomalies could also be observed in depression using an appropriate tool such as manual line bisection; 3/performances in the MVPT-V suggested that a simple visual-perceptual deficit could not explain the lateralized anomaly observed in the manual line bisection, as it is the case in the hemineglect syndrome.

Serotonergic response to stress: a protective factor against abnormal dopaminergic reactivity in schizophrenia?

In a double-blind-crossover-study, 10 patients with schizophrenia, 10 of their unaffected siblings and 9 healthy controls randomly received metabolic stressor and placebo. A significant HVA plasma elevation in response to stress was found in siblings whose response was intermediate to that of patients and controls. Only siblings additionally displayed an exaggerated 5HIAA response.

Pseudoneglect in schizophrenia: a line bisection study with cueing.

INTRODUCTION: Numerous authors have reported the existence of lateralised abnormalities towards the right side in patients with schizophrenia. METHODS: In the present study, a manual line bisection task was used to assess the existence of a visuospatial bias in patients with schizophrenia as compared to healthy subjects and left unilateral neglect patients. In addition, we used a local cueing paradigm (consisting of a number placed on the right, on the left, or at both ends of the line). RESULTS: Healthy subjects showed a leftwards trend in the "no cue" condition (known as pseudoneglect) and neglect patients showed a right bias in all cue conditions. In contrast, patients with schizophrenia placed their manual estimation of the centre further to the left than healthy subjects in all cue conditions, reflecting neglect of the right side of the line. Moreover, like healthy subjects and neglect patients, patients with schizophrenia were affected by the local cueing. CONCLUSION: Hence, patients with schizophrenia show a bias in their spatial representation, which does not interfere with local context processing.

Exaggerated leftward bias in the mental number line of patients with schizophrenia.

Several visuo-motor tasks can be used to demonstrate biases towards left hemispace in schizophrenic patients, suggesting a minor right hemineglect. Recent studies in neglect patients used a new number bisection task to highlight a lateralized defect in their visuo-spatial representation of numbers. To test a possible lateralized representational deficit in schizophrenia, we used the number bisection task in 11 schizophrenic patients compared to 11 healthy controls. Participants were required to orally indicate the central number of an interval orally presented. Whereas healthy subjects showed no significant bias, schizophrenic patients presented a significant leftward bias. Therefore, these results suggest an impairment in higher order representations of the number space in patients with schizophrenia, an impairment that is qualitatively similar to the deficit described in neglect patients.

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.

Autism and developmental delay: a comparative clinical study in very young children using IBSE scale.

OBJECTIVE: This study improves the knowledge of early autistic symptomatology and research concerning (i) the significant differences in the behaviors of children with autistic disorder (AD) and children with a developmental delay (DD), and (ii) the influence of the cognitive delay on symptomatology. METHOD: Two groups of 20 young children (7-42 months) were compared: children with AD, and those with DD. The groups were paired by chronological and developmental age. The comparison was extended to four subgroups composed according to age (younger and older children--<24 months, >24 months) and to the global development quotient (GDQ) (the more and less delayed). Each child was evaluated with the Infant Behavior Summarized Evaluation scale (IBSE). RESULTS: For the younger AD children, significant differences affected social communication and their adaptation to the environment (intolerance to frustration, resistance to change). For the older children (>24 months), this study showed the rapid progression of the number of distinctive signs between AD and DD children according to age and/or developmental level. CONCLUSIONS: Cognitive delay has an important influence on the symptomatology at the moment of initial recognition of an autistic syndrome. This study is a complement for the fuller understanding of the nature and early diagnosis of disorders specific to autism at the earliest phases of development.

Source monitoring deficits in hallucinating compared to non-hallucinating patients with schizophrenia.

In two source memory tests, hallucinating patients with schizophrenia (N=30), compared to non-hallucinating (N=31), are impaired in recognizing internal self-generated items and misattribute them to an external event. They are not impaired in recognizing events from two internal sources. Results support a selective source-monitoring deficit in the occurrence of auditory hallucinations.

[Wiscosin card sorting task in patients with schizophrenia and thier siblings]. / Test Wisconsin chez les patients souffrant de schizophrénie, et leurs frères et soeurs.

OBJECTIVE: This study's first objective was to confirm that patients with schizophrenia and their nonmentally ill siblings share the same impaired executive function when compared to healthy control subjects. The second objective was to study the relation between Wisconsin card sorting task (WCST) performance and the persistence and severity of clinical symptoms, as well as different clinical dimensions. METHOD: Ninety subjects were involved in this study, divided in 3 groups of 30 each: one group of patients with schizophrenia, one group of their siblings, and a control group. Symptom severity was assessed with the Positive and Negative Syndrome Scale (PANSS), and social functioning was measured by the Global functioning scale (GFS). The WCST was administered to all 3 groups. RESULTS: Patients with schizophrenia and their siblings had a significantly lower WCST performance than control subjects. Statistical analysis showed that the patient group had a significantly greater impaired WCST performance than the 2 other groups. Siblings also had a significantly lower performance than the control subjects. Furthermore, no significant relation was found between WCST performance and other variables, including age, gender, education, illness duration, treatment, and different PANSS and GFS scores. CONCLUSION: Patients with schizophrenia and their nonmentally ill siblings share the same impaired executive function. These findings suggest that WCST performance can be considered a schizophrenia vulnerability marker in siblings of patients with schizophrenia.

Low frequency repetitive transcranial magnetic stimulation improves source monitoring deficit in hallucinating patients with schizophrenia.

Auditory hallucinations have been associated with a disruption in monitoring one's own speech suggesting an autonoetic agnosia in schizophrenia. This deficit can be measured by a source monitoring task. Low frequency transcranial magnetic stimulations (rTMS) applied to the left temporoparietal cortex can inhibit cortical areas involved both in autonoetic agnosia (which means 'the inability to identify self-generated mental events') and in auditory hallucinations (AH) phenomena. Although improvements in AH have been repeatedly reported following rTMS treatment, effects on autonoetic agnosia measured by source monitoring have never been investigated. We aimed to investigate the relation between improvements in AH and source monitoring performance after rTMS treatment. Twenty four right-handed refractory schizophrenic patients with hallucinations randomly received sham or active 10.0001-Hz rTMS to the left temporoparietal cortex and performed 2 source monitoring tasks requiring discrimination between silent- and overt-reading words before and after rTMS sessions. Compared to sham, active rTMS significantly improved AH. Source monitoring performances and the improvements tended to correlate, which would support a specific relation between autonoetic agnosia and auditory hallucinations.

Facial expression and sex recognition in schizophrenia and depression.

BACKGROUND: Impaired facial expression recognition in schizophrenia patients contributes to abnormal social functioning and may predict functional outcome in these patients. Facial expression processing involves individual neural networks that have been shown to malfunction in schizophrenia. Whether these patients have a selective deficit in facial expression recognition or a more global impairment in face processing remains controversial. OBJECTIVE: To investigate whether patients with schizophrenia exhibit a selective impairment in facial emotional expression recognition, compared with patients with major depression and healthy control subjects. METHODS: We studied performance in facial expression recognition and facial sex recognition paradigms, using original morphed faces, in a population with schizophrenia (n=29) and compared their scores with those of depression patients (n=20) and control subjects (n=20). RESULTS: Schizophrenia patients achieved lower scores than both other groups in the expression recognition task, particularly in fear and disgust recognition. Sex recognition was unimpaired. CONCLUSION: Facial expression recognition is impaired in schizophrenia, whereas sex recognition is preserved, which highly suggests an abnormal processing of changeable facial features in this disease. A dysfunction of the top-down retrograde modulation coming from limbic and paralimbic structures on visual areas is hypothesized.

Effects of emotion and identity on facial affect processing in schizophrenia.

We used facial affect labeling and matching tasks to study effects of (1) emotion and (2) identity on facial affect processing in patients with remitted schizophrenia (n=30) compared with healthy controls (n=30). The patients (1) had a specific deficit for labeling facial affects of sadness and anger but not happiness, disgust and fear; they (2) performed as well as controls in matching facial affects in one face but were impaired in matching facial affects in two different faces. The patients' impairment in facial affect processing may be emotion-specific. The effects of identity on facial affect processing are discussed in the light of several hypotheses (a deficit of context processing, a global-local processing impairment or a selective attention deficit), and may be related to frontal, prefrontal or amygdala dysfunctions.

Slow transcranial magnetic stimulation can rapidly reduce resistant auditory hallucinations in schizophrenia.

BACKGROUND: Almost a quarter of patients with schizophrenia present with resistant auditory verbal hallucinations (AVH), a phenomenon that may relate to activation of brain areas underlying speech perception. Repetitive transcranial magnetic stimulation (rTMS) at 1 Hz reduces cortical activation, and recent results have shown that 1-Hz left temporoparietal rTMS may reduce AVH. The aim of this study was to replicate recent data and investigate whether low-frequency rTMS with a high total stimulation number delivered in a shorter 5-day block produces similar benefit. METHODS: Ten right-handed schizophrenia patients with resistant AVH received 5 days of active rTMS and 5 days of sham rTMS (2,000 stimulations per day at 90% of motor threshold) over the left temporoparietal cortex in a double-blind crossover design. The two weeks of stimulation were separated by a 1-week washout period. RESULTS: AVH were robustly improved (56%) by 5 days active rTMS, whereas no variation was observed after sham. Seven patients were responders to active treatment, five of whom maintained improvement for at least 2 months. CONCLUSIONS: These data confirm the efficiency of low-frequency rTMS applied to the left temporoparietal cortex, compared with sham stimulation, in reducing resistant AVH. This improvement can be obtained in only 5 days without serious initial adverse events.

Hidden cardiac lesions and psychotropic drugs as a possible cause of sudden death in psychiatric patients: a report of 14 cases and review of the literature.

OBJECTIVE: To confirm the hypothesis that psychotropic drugs, especially neuroleptics, lithium, and antidepressants, are implicated as a cause of unexpected sudden death in psychiatric patients because of their cardiotoxicity, especially when hidden cardiac lesions are present. METHOD: We performed a full pathological examination of 14 psychiatric patients who unexpectedly and suddenly died between 1980 and 1999. RESULTS: Neuroleptics were involved in 13 instances, antidepressants in 9, and anxiolytics in 5. Psychotropic drugs were combined in all but a single patient. In all 14 patients, toxicological analyses discarded drug overdose as cause of death. At postmortem examination, the brain and abdominal organs were normal. In 13 patients, the following lesions were found in the heart and lungs: dilated cardiomyopathy (6 patients), left ventricular hypertrophy (2 patients, 1 of which was associated with mitral prolapse and anomalies of His bundle), arrhythmogenic cardiopathy of the right ventricle (1 patient), pericarditis (1 patient), mitral prolapse (1 patient), muscular bridge on the anterior interventricular artery (1 patient), and Mendelsons syndrome (1 patient). In 1 case, no changes were seen. Most of the drugs that were taken immediately prior to death can induce arrhythmias either by prolonging the QT interval, potentially resulting in torsades de pointes, or by widening QRS complexes, possibly leading to reentry and ventricular fibrillation. CONCLUSION: Our findings suggest that the arrhythmogenic effects of psychotropic drugs can be exacer bated when preexisting hidden cardiac lesions are present and can result in sudden death. Patients should be systematically evaluated for cardiac lesions prior to starting any treatment with psychotropic drugs; the minimal effective dosage should be used.

Left temporoparietal transcranial magnetic stimulation in treatment-resistant schizophrenia with verbal hallucinations.

Left temporoparietal repetitive transcranial magnetic stimulation (rTMS) reportedly diminishes verbal hallucinations. A 21-year-old schizophrenic man, who had killed his mother in the belief that she was a demon, failed to respond to combined treatment with a variety of antipsychotic agents. His persistent hallucinations consisted of two voices (God and the Devil). As an adjunct to continued antipsychotic medication, the patient received a course of rTMS: 10 sessions of 1-Hz stimulations near Wernicke's area. After rTMS, the patient's hallucinations grew less intrusive and he no longer required isolation. Although the improvement could be a delayed effect of medication, further trials of rTMS in cases of this type appear justified.

Fluvoxamine versus fluoxetine in major depressive episode: a double-blind randomised comparison.

A double-blind, multinational study was conducted to compare the efficacy and safety of fluvoxamine and fluoxetine in outpatients with major depressive episode; 184 patients were randomised to fluvoxamine (100 mg/day) or fluoxetine (20 mg/day) for 6 weeks. Both drugs were effective and there were no statistically significant differences between them in the area under the curve of change from baseline in the Hamilton depression rating scale (HAMD) total score. However, the percentage of HAMD responders (>or= 50% decrease in HAMD total score) at week 2, the clinical global improvement severity of illness score at week 2 and the depression subscale of the irritability, depression and anxiety scale at weeks 1, 2 and 4, all showed significant advantages for fluvoxamine. During the last 2 weeks, fluvoxamine was significantly more effective in improving the HAMD sleep disturbance scale. Both drugs were well tolerated and there were no marked differences in their side effect profiles which were typical of SSRIs. Fluvoxamine and fluoxetine have similar efficacy and safety profiles in the treatment of major depressive episode; the findings of this study indicate that fluvoxamine may have a faster onset of action with respect to resolution of depressive symptoms and result in a better improvement in sleep quality.

[Validation of the French version of the Raine schizotypal personality questionnaire in a population of Tunisian students]. / Validation de la version française du questionnaire de personnalite schizotypique de Raine en population estudiantine Tunisienne.

Schizotypal personality disorder is considered as a marquer of schizophrenia proneness. In opposition at other self report measures of schizotypal personality disorder, the "Schizotypal Personality Questionnaire" (SPQ) developed by Raine, assesses all nine features of this disorder. The aims of this study is to present the validation on the French version of the SPQ on Tunisian student sample. It consists on a transversal study directed from April to may 2000. The sample was compound of 198 healthy and voluntary students from the medical university of Monastir. The questionnaire has a high internal reliability (SPQ total: Cronbach's alpha = 0.91; SPQ nine subscales: Cronbach's alpha = 0.59 to 0.74). The ten percent high and low cutoffs for the top and the bottom ten percents of SPQ scores were respectively 42/74 and 10/74 for women, 42/74 and 7/74 for men and 42/74 et 9/74 for total sample. A principal component analysis revealed two main factors or dimensions of schizotypal personality disorder in our sample: positive dimension (made up of ideas of reference, magical thinking and unusual perceptual experiences) and a negative dimension (made up of no close friends, social anxiety and blunted affect). Our results were closely similar to these found by Raine and, other validation studies with SPQ. However some sociocultural aspects were found in our study.

Validity of the depressive dimension extracted from principal component analysis of the PANSS in drug-free patients with schizophrenia.

Depressive symptoms frequently occur during the course of schizophrenia. This study explored the relationships between the schizophrenia symptomatology and three measures of depression. Eighty-one drug-free inpatients with acute schizophrenia were assessed with the positive and negative syndrome scale (PANSS), the Calgary depression scale for schizophrenia (CDSS), and the Hamilton rating scale for depression (HAM-D). The depressive subscale of PANSS (PANSS-D) was also considered as a third scale for measuring depression. A principal component analysis (PCA) of PANSS items identified five clinical dimensions of schizophrenia called 'negative', 'positive', 'anxio-depressive', 'excitement', and 'disorganisation and others'. Our anxio-depressive dimension (PANSS-ad) was strictly identical with the PANSS-D. Scores on CDSS and HAM-D were highly inter-correlated and highly correlated with the PANSS-ad. Furthermore, while scores on CDSS were correlated only with this dimension, scores at HAM-D were also positively correlated with the negative dimension and negatively correlated with the excitement dimension. In conclusion, our results suggest that PANSS evaluation itself may be sufficient to give a correct approximation of the depression in patients with schizophrenia. However, depression scales are of course needed to assess specifically depressive symptoms in patients with schizophrenia; hence, the CDSS could be a more specific instrument than HAM-D.