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).

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.

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.

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.

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.

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.

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.

Gaze direction determination in schizophrenia.

It has been proposed that an impairment in gaze determination is responsible for the paranoid symptoms reported in schizophrenia. To address this, we examined the gaze discrimination system in schizophrenia. Thirty-two patients suffering from schizophrenia (20 patients with persecutory delusions and 12 patients without such delusions) were compared to 32 control subjects on two specific tasks. In the first task, the subjects had to determine whether 130 portraits were looking right or left. In the second task the subjects were asked to determine whether or not 130 portraits were looking at them. The absolute threshold of difference used to investigate the influence of instruction on gaze discrimination did not show any difference between patients with schizophrenia, whatever paranoid or not, and control subjects. Paranoid patients, as well as controls, displayed a significantly finer discrimination threshold in the right vs. left judgment than in the self vs. non-self judgment. Subjects with schizophrenia were able to discriminate gaze direction in the two tasks, but they took significantly more time in the task requiring to determine the presence or the absence of a mutual gaze contact than in the other one, whereas controls took the same duration to elicit both tasks. These data are consistent with those reporting that perceptual abilities are spared in schizophrenia while delusions are related to an impairment of a higher level of analysis.

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.

Exploring imagined movements in patients with schizophrenia.

Patients with schizophrenia demonstrate impairments indicative of an inability to accurately monitor internally generated images. Motor imagery measures the ability to generate internal images of intended but not executed motor movements. Ten patients with schizophrenia completed actual and imagined versions of a pointing task with a well defined speed-accuracy trade-off function. For controls, movement time increases as target size decreases for both actual and imagined movements. Despite showing the expected speed-accuracy trade-off for actual movements, the imagined movements of schizophrenics showed no reliable relationship to target size. This was true for each patient and appeared to be independent of symptom profile. These results suggest that patients with schizophrenia are unable to generate accurate internal images of their own motor movements.

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.

Cannabis use correlates with schizotypal personality traits in healthy students.

The literature suggests that cannabis use and schizotypal traits both constitute risk factors for the later development of schizophrenia. However, their interrelationships remain to be evaluated. The present study examined the association between cannabis use and schizotypal traits in 232 healthy students who ranged in age from 18 to 25 years. All the students had completed the Schizotypal Personality Questionnaire and four of the Chapman Psychosis Proneness Scales: the Magical Ideation Scale; the Perceptual Aberration Scale; the Revised Physical Anhedonia Scale; and the Revised Social Anhedonia Scale. Subjects were divided into three groups according to cannabis use typology: those who had never used cannabis, those who were past or occasional users, and those who were regular users. Higher scores on the Schizotypal Personality Questionnaire and the Magical Ideation Scale characterized the regular and past or occasional users compared with those who had never used cannabis. The co-occurrence of cannabis use and schizotypal traits appeared to be independent of anxiety and depression dimensions. These data suggest that cannabis use and schizotypal traits have to be jointly considered in further longitudinal studies of schizophrenia risk factors.

[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.

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.

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.

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.

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.

[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.