Poor performance in smooth pursuit and antisaccadic eye-movement tasks in healthy siblings of patients with schizophrenia.

This study examines the area of eye movement dysfunctions as an indicator of vulnerability to schizophrenia. Eye movement performance was investigated with three different paradigms: Smooth Pursuit Eye Movements (SPEM); Visually Guided Saccades (VGS); and Antisaccades (AS) in 21 clinically stable patients with schizophrenia, 21 of their healthy, biological full siblings and 21 healthy control subjects. The three groups did not differ on VGS performance, whereas both patients and their siblings showed lower SPEM gain, an increased catch-up Saccades (CUS) rate, reduced AS accuracy and an increased number of AS errors in comparison to control subjects. In addition, patients with schizophrenia exhibited increased AS latency. Among the patients with schizophrenia, eye movement abnormalities did not correlate with age, gender, clinical state or duration of illness. These data suggest that abnormalities of SPEM and AS may represent neurobiological markers of the vulnerability to schizophrenia in individuals at high genetic risk for the disease.

Neuropsychological deficit in siblings discordant for schizophrenia.

This study was aimed, first, at detecting neuropsychological markers that assess vulnerability to schizophrenia in siblings of patients with schizophrenia, and second, at exploring possible relationships between markers. For these purposes, performances were assessed in 18 clinically stabilized patients with schizophrenia, 18 of their unaffected full siblings, and 15 controls on attentional abilities (the Degraded Stimuli-Continuous Performance Task [DS-CPT] and the Span of Apprehension [SOA] task) and on executive functions (the Wisconsin Card Sorting Test [WCST]). Both patients and siblings were impaired on the three tasks, leading to the conclusion that these poor performances may represent markers of genetic vulnerability to schizophrenia. Furthermore, significant relationships were found between DS-CPT and WCST performance in patients only, suggesting a possible implication of prefrontal brain areas for the two tasks. In spite of the lack of similar relationships between DS-CPT and WCST in siblings, this raises the question of a putative role of prefrontal areas in vulnerability to schizophrenia.

[Vulnerability to schizophrenia. III: Importance and limits of the Identical Pairs Continuous Performance Test]. / Vulnérabilité à la schizophrénie. III: Intérêts et limites du test de performances continues à paires identiques (CPT-IP).

Since several investigations have shown attentional deficits both in patients with schizophrenia and in subjects at high risk for schizophrenia, these deficits could be valuable vulnerability markers for schizophrenia. The aim of this study was to investigate wether non psychotic relatives of schizophrenic probands have deficits in sustained attention as measured by the Continuous Performance Test, Identical Pairs (CPT-IP) version. The study subjects were 25 schizophrenic probands, 50 of their first-degree relatives and 46 normal controls. For each subject, attention was assessed during 6 experimental conditions (2 standard, 2 slow, 2 easy conditions) of visual stimuli (digit-numbers and shapes). In each of the six conditions, the value of the sensitive index d' in the first-degree relative group was at an intermediate level between the patient and control groups. Moreover, in the standard shape condition, the d' value was significantly lower in the schizophrenic and in the relative groups than in the control group. This deficit was all the more interesting since it was not explained by a deficit in general intellectual abilities or by psychopathology such as anxiety or depression. Furthermore, the schizophrenic patients made more random errors in the standard and in the slow number conditions than both other groups. All groups improved their performance when the stimulus duration increased and when the processing load decreased. As a conclusion, this investigation seems: 1) to confirm the existence of an attentional deficit in the first-degree relatives of patients with schizophrenia; 2) to demonstrate the interest of the CPT-IP to detect this deficit. It must be emphasized that in order to detect the deficit, one only needs to explore the standard shape condition and that under such circumstances, the CPT-IP test has the advantage of being less time consuming than tests used in previous studies.

Alteration of event related potentials in siblings discordant for schizophrenia.

This study was aimed at confirming that auditory event related potential (ERP) abnormalities are indicators of vulnerability to schizophrenia. Auditory ERP performances were assessed at Fz, Cz, and Pz, with an oddball paradigm, in 21 clinically stable patients with schizophrenia, 21 of their healthy biological full siblings and 21 control subjects. The evoked response did not differ between the three groups on N200 waves. Compared to controls, patients with schizophrenia exhibited reduced amplitudes of N100 and P300, and prolonged latency of P300, while their siblings showed prolonged latency of P200 and P300. Among the patients with schizophrenia, ERP abnormalities did not correlate with age, clinical state, duration of illness or antipsychotic treatments. Although other conditions also accounted for alterations of the same type, ERP abnormalities may represent a neurobiological marker of the genetic vulnerability to schizophrenia, independent of phenotypic expression.

[Acute exacerbations in schizophrenia]. / Les exacerbations aiguës dans la schizophrénie.

In a context of acute psychotic episodes, the occurrence of acute exacerbations offers an interesting perspective on the long-term progression of schizophrenia, which has for too long been considered as a chronic illness. The most recent clinical and epidemiological data confirm the episodic progression of this illness. These data concerning progression have given rise to a proposed model of vulnerability to psychosis. The appearance of the first signs of such an exacerbation in a hitherto stabilised patient requires the immediate institution of medico-psycho-social management strategies for the treatment of this new episode. It has been amply demonstrated that long-term maintenance therapy considerably reduces the risk of relapse. Using this model, a number of authors have proposed that schizophrenia be considered as the outcome of an interaction between permanent vulnerability of multifactorial origin and stress factors. In this theory, only episodic decompensation, and thus acute exacerbation, is modeled rather than the entire schizophrenic pathology. Patients living in families with low emotional expression exhibit a lower range (13%) of relapse than those living in families that are highly emotionally expressive.

Attentional deficits in patients with schizophrenia and in their non-psychotic first-degree relatives.

The aim of this study was to investigate whether non-psychotic relatives of schizophrenic probands have deficits in sustained attention as measured by the Continuous Performance Test, Identical Pairs version (CPT-IP) and whether such deficits are associated with negative schizotypal personality disorders. The study subjects were 23 schizophrenic probands, 45 of their first-degree relatives and 36 normal controls. For each subject, attention was assessed during five conditions (2 standard, 2 slow, 1 easy) of visual stimuli (numbers and shapes). Schizotypy status was determined with the physical anhedonia and social anhedonia scales of Chapman et al. (Chapman, L.J., Chapman, J.P., Raulin, M.L., 1976. Scales for physical and social anhedonia. Journal of Abnormal Psychology 42, 374-382). The CPT-IP sensitive index d' in the standard shape condition was significantly lower in schizophrenics and in their relatives than in controls. For all d' values, the percentage of impaired first-degree relatives was at an intermediate level between patients and control individuals. Furthermore, the schizophrenic probands made more random errors in the standard and in the slow number conditions than the other two groups. None of the schizotypy measures correlated with the CPT-IP deficits. These results suggest that spatial sustained attention deficit may be a vulnerability marker for schizophrenia; however, this deficit and the negative dimension of schizotypal personality disorders may be distinct traits.

Evaluation of endozepine-like immunoreactivity in the frontal cortex of suicide victims.

Diazepam-binding inhibitor (DBI) and its processing products, including the octadecaneuropeptide (ODN), are polypeptides called endozepines which have multiple biological effects, including regulation of mitochondrial steroidogenesis and modulation of GABA-gated chloride channels. Concentrations of ODN-like immunoreactivity (ODN-Li) were measured by radioimmunoassay in the frontal cortex of nine drug-free suicides and nine drug-free sudden-death victims. The level of ODN-Li was higher in the right than in the left frontal cortex, in both suicide (p < 0.05) and control (p < 0.02) subjects. No significant differences were found between suicides and controls either in the right and left cortex, or when considering the gender and the post-mortem diagnosis of depression.

Cerebral investigation of healthy siblings of schizophrenics.

Computed tomography (CT) studies have demonstrated that lateral ventricular size measured by ventricular brain ratio (VBR), as well as third ventricle width, is statistically enlarged in schizophrenics. Moreover, these cerebral abnormalities differ according to symptomatology evaluated with a positive and negative symptom scale. The aim of this study was to investigate, using CT scans, healthy siblings of schizophrenics, and relate the results to their ill siblings. Nineteen healthy siblings of 12 previously studied schizophrenics underwent CT scans, which were compared to those of their related schizophrenic sibling and to 17 unrelated control subjects. The results showed that in ten of 12 families, schizophrenics have larger ventricles (lateral and third ventricles) than their healthy siblings. Ventricular enlargement of healthy siblings was correlated with severity of negative symptoms of their ill sibling. Implications of a familial contribution for ventricular size and negative symptoms are discussed.

No season-of-birth effect in schizophrenic patients from a tropical island in the Southern Hemisphere.

The distribution of birth rates was examined in 668 schizophrenic patients born in Réunion, a tropical French island in the Southern Hemisphere, and compared with that in the general local population. We failed to observe a significant season-of-birth effect, either in the total sample of schizophrenic patients or in subgroups categorized by gender, age, or family history of schizophrenia. Seasonal factors do not appear to affect the yearly distribution of births among schizophrenic patients on Réunion Island. It is nevertheless possible that environmental factors which are seasonal in countries with more contrasting climates have a continuous effect, throughout the whole year, in subtropical areas. Conversely, these findings provide some evidence against the hypothesis that there is an age-incidence artifact in seasonal studies from countries in the Northern Hemisphere.

Increased serum levels of neuron-specific enolase in epileptic patients and after electroconvulsive therapy--a preliminary report.

Serum neuron-specific enolase (NSE) levels were studied by an enzymo-immunoassay method in 2 groups of patients: a group of epileptic patients, and a group of patients with refractory major depression after electroconvulsive therapy (ECT). In patients without organic neurological disease (n = 274) the mean serum NSE level (+/- S.D.) was 8.4 +/- 3.4 micrograms/l. No correlation with sex or age was observed. No significant difference was observed between epileptic patients without seizure or major electroencephalogram (EEG) abnormality, and a reference group. Significant increases were observed in 32 samples collected from patients with interictal EEG without spikes and waves before the 7th day after a seizure, in whom mean NSE was 21.5 +/- 9.4 micrograms/l, and in 26 samples from 4 patients without seizures but with spikes and waves in the interictal EEG, whose mean NSE was 20.6 +/- 11.5 micrograms/l. The increases of serum NSE levels in epileptic patients seem therefore to be linked to seizures and/or to EEG abnormalities. The consequences of these observations for the survey of epileptic patients, and for the diagnosis of cerebral tumors (mainly neuroblastoma) or for monitoring treatment after surgical resection, are discussed. In only 1 patient out of 6, an increase in serum NSE levels was observed with a peak about 12 h after ECT. No significant correlation with the ECT features (length of seizures, one- or two-sided electrodes) was observed.

[Depression in children. Etiological, clinical and therapeutical aspects]. / La dépression de l'enfant. Aspects étiologiques, cliniques et thérapeutiques.

Although the concept of child depression is today well admitted, the diagnosis of childhood depression remains difficult due to the variety of its symptoms, many of them being non specific, and the frequency of masked depression. For each period of child development, ie: infancy, early childhood, late childhood and adolescence, depression has particular clinical characteristics which are important to be known for its early recognition. Depression in a child frequently appears to result from the conjunction of a constitutional predisposing ground, one or several losses, and an inappropriate parental response. One must be concerned about the major risk of deleterious effects on psychoaffective, intellectual and somatic development of neglected depression, so that its prevention, early recognition, and treatment are mandatory. According to the cases, treatment requires individual or familial psychotherapy and chemiotherapy, and in particular cases care in a medico-educative establishment.

Seasonality of birth and ventricular enlargement in chronic schizophrenia.

Many studies have established that birth dates during the winter and early spring months are more common in schizophrenic patients than in the general population. It has been hypothesized that children born in winter are more likely to be exposed to environmental factors which could lead to the development of schizophrenia later in life. Another finding of interest has been the demonstration in brain-imaging studies that mild ventricular enlargement is more often found in schizophrenic patients than in healthy control subjects. In the present report, an increased incidence of ventricular enlargement was found in schizophrenic patients born in the winter months. Although the relationship between seasonality of birth and brain abnormalities is unclear, these phenomena could be partly linked.

[Psychotropic drugs in child and adolescent psychiatry]. / Les psychotropes en psychiatrie de l'enfant et de l'adolescent.

Although there has been concern about the use of psychoactive drugs in children, evidence is accumulating that these drugs are beneficial. The various groups of currently available drugs are reviewed with their pharmacological characteristics, adverse effects, dosages, and uses in children. Benzodiazepines, both widely used and severely criticized, are effective when used correctly, in particular for the shortest possible length of time. Antidepressants are indicated in many conditions including depression, obsessive-compulsive disorders, and anxiety; some of their indications are specific to children, such as separation anxiety, enuresis, and school phobia. Neuroleptics have a less well defined role and are usually given as symptomatic treatment, although their use is limited by their side effects. This is also true of lithium, despite fairly good tolerability in children. Carbamazepine was introduced in psychiatry too recently to allow valid evaluation. Psychostimulants are viewed with fear in France despite their documented efficacy in hyperkinetic children. A few other drugs used in other fields of medicine are currently being investigated in psychiatry (beta-blockers, clonidine, naloxone). A debate on drugs used in child psychiatry is much needed in particular to overcome the methodological and ethical problems raised by controlled trials of which few have been conducted to date. Drug therapy should be combined with psychotherapy to place the target symptoms in perspective with regard to the child's overall make-up.

Long-term isolation of Wistar rats alters brain monoamine turnover, blood corticosterone, and ACTH.

In this work, we investigated neurochemical parameters in the brain of male Wistar rats after isolation times (13 weeks) longer than those previously reported with this strain: a large majority of animals became muricidal under these conditions. Changes in monoamines turnover in hippocampus, cortex, and cerebellum and, in the blood, ACTH, and corticosterone were investigated. Monoamine turnover was analysed using two different approaches: first, by measuring neurotransmitter and metabolite levels and second, by measuring rate of accumulation of the precursor after decarboxylase. Both methods revealed a significant increase in catecholamine turnover in the three regions studied after the 13-week isolation; in contrast, only a modest elevation of 5-hydroxytryptophan accumulation was obtained in cortex and cerebellum of isolated rats. We also observed a decrease in corticosterone levels in blood concomitant with an increase of ACTH.

Benzodiazepine binding sites and their modulators in hippocampus of violent suicide victims.

Benzodiazepine binding sites were studied by autoradiography in several hippocampic layers in brains of drug-free violent suicide victims (hanging) and matched controls. Kd was increased in suicides, and when brain sections from control subjects were incubated in the bath fluid that had previously served to incubate sections from suicides, Kd was increased in the same way. Results are discussed in terms of possible modulators of benzodiazepine binding sites, mainly tissue GABA and amino acid concentrations.

Relationship between symptoms rated with the Positive and Negative Syndrome Scale and brain measures in schizophrenia.

The Positive and Negative Syndrome Scale (PANSS) was used to rate clinical symptoms in 42 inpatients with schizophrenia before they were examined by computed tomography. Significantly higher mean size of lateral and third ventricles, and higher mean cortical atrophy were found in schizophrenic patients compared with healthy control subjects. Ventricular enlargement and cortical atrophy were significantly related to low scores on the Composite subscale of the PANSS. Positive correlations were observed mainly with negative items such as blunted affect, emotional withdrawal, difficulties in abstract thinking, passive-apathetic social withdrawal, and lack of spontaneity of conversation. Additional positive correlations were observed with two items from the General Psychopathology subscale (mannerisms and disorientation). Inverse correlations were found with most positive items. These results suggest a relationship between brain structural abnormalities and the symptomatology of schizophrenia recorded with PANSS.

Quantitation by gas chromatography with selected-ion monitoring mass spectrometry of "natural" diazepam, N-desmethyldiazepam and oxazepam in normal human serum.

During the past five years, the literature has tended to prove the occurrence of "natural benzodiazepines" in tissues and biological fluids of non-medicated humans. Several have been identified but very few papers deal with their quantitation in biological material. We present here a method for the specific and sensitive measurement of serum levels of diazepam, N-desmethyldiazepam and oxazepam by gas chromatography with selected-ion monitoring mass spectrometry in twenty human volunteers without medication. Diazepam was found over the whole population, in the range 7.3-32.0 pg/ml, identical in males and females. The other two were present in only some individuals (1.0-7.6 pg/ml for N-desmethyldiazepam and 2.0-13.0 pg/ml for oxazepam). The origin (endogenous, dietary or microbial) of these substances is still to be elucidated.

[X-ray computed tomographic abnormalities in schizophrenia. Trial of relationship with clinical data]. / Anomalies tomodensitométriques dans la schizophrénie. Tentatives de corrélations avec les données cliniques.

Computerized tomography (CT-scan) studies in schizophrenia revealed that some patients have neuromorphological abnormalities. The structural changes consist mainly in lateral and third ventricle enlargement, and in cortical atrophy. The present study evaluates these three changes in 42 schizophrenics aged 18 to 50, compared to 24 healthy controls. Diagnosis were established from information gathered by personal interview with the SADS-LA. Clinical sub-types were evaluated according to the DSM III-R criteria. Moreover, detailed symptoms were rated according to the Positive And Negative Syndrome Scale (PANSS). CT scans were recorded in floppy disks and blindly analyzed. Schizophrenics shown significant higher mean size of lateral and third ventricles, and higher mean anterior cortical atrophy than healthy subjects. Significant differences were also found between subtypes, with more marked abnormalities in the disorganized group. The relationship between brain abnormalities and clinical symptoms recorded with the PANSS, were analysed using Pearson correlates. Positive correlations concerned mainly negative symptoms like blunted affect, emotional withdrawal, difficulties in abstract thinking, passive apathetic social withdrawal and lack of spontaneity of conversation. Positive correlations are also observed with some symptoms classified with the PANSS in the General Psychopathology scale such as mannerism and disorientation. Negative correlation concerned most of PANSS positive symptoms.