The Charles Bonnet syndrome (CBS) is a condition associated with complex visual hallucinations occurring in the elderly in patients with visual impairment and normal mental health. Here, we report the case of a 78-year-old woman who has a limited visual acuity with a CBS that we postulated to be in relationship to a vitamin B12 deficiency. This case is the first report of vitamin B12 deficiency-associated CBS.

Les hallucinations acousticoverbales constituent des symptômes positifs extrêmement fréquents de la schizophrénie à début précoce. Ces symptômes sont d'autant plus invalidants qu'ils sont souvent pharmacorésistants. Les procédures de stimulation magnétique transcrânienne répétée (SMTr) utilisées dans ce cas chez les sujets schizophrènes adultes ont montré une bonne efficacité et tolérance. Nous présentons ici le cas d'un enfant de 11 ans avec un diagnostic de schizophrénie à début très précoce comprenant un syndrome hallucinatoire floride et un syndrome massif d'automatisme mental. Le syndrome hallucinatoire résistant aux traitements antipsychotiques de cet enfant a pu être considérablement réduit par dix sessions de SMTr, le rendant plus accessible à la prise en charge psychothérapeutique et permettant sa rescolarisation. La SMTr constitue une option thérapeutique prometteuse de l'épisode hallucinatoire de l'enfant schizophrène, dont il faut désormais définir la place dans les stratégies thérapeutiques de la schizophrénie à début précoce.Auditory-Verbal Hallucinations (AVH) constitute extremely frequent positive symptoms in early-onset schizophrenia. These symptoms are all the more invalidating as they are often drug-resistant. The procedure of repetitive transcranial magnetic stimulation (rTMS), used in such cases in adult subjects with schizophrenia, showed good efficiency and tolerability. We present here the case of an 11-year-old child with a diagnosis of very-early onset schizophrenia including florid AVH and a massive delusion of alien control. His hallucinatory syndrome resistant to the antipsychotic treatments was considerably reduced by rTMS. This treatment allowed this child to attend school and to follow regular psychotherapeutic sessions. The spectacular and rapid response to rTMS reported here indicates that rTMS should occupy in future years a key role in the treatment of AVH in very early onset schizophrenia.

DNA sequence variations within the 22q11 DiGeorge chromosomal region are likely to confer susceptibility to psychotic disorders. In a previous report, we identified several heterozygous alterations, including a complete deletion, of the proline dehydrogenase (PRODH) gene, which were associated with moderate hyperprolinemia in a subset of DSM III schizophrenic patients. Our objective was (i) to determine whether hyperprolinemia is associated with increased susceptibility for any of three psychiatric conditions (schizophrenia, schizoaffective disorder and bipolar disorder) and (ii) to establish a correlation between hyperprolinemia and PRODH genotypes. We have conducted a case-control study including 114 control subjects, 188 patients with schizophrenia, 63 with schizoaffective disorder and 69 with bipolar disorder. We report that, taking into account a confounding effect due to valproate treatment, hyperprolinemia is a risk factor for DSM IIIR schizoaffective disorder (P=0.02, Odds ratio=4.6, 95% confidence interval 1.3-16.3). We did not detect 22q11 interstitial deletions associated with the DiGeorge syndrome among the 320 patients of our sample and we found no association between common PRODH polymorphisms and any of the psychotic disorders. In contrast, we found that five rare PRODH alterations (including a complete PRODH deletion and four missense substitutions) were associated with hyperprolinemia. In several cases, two variations were present simultaneously, either in cis or trans in the same subject. A total of 11 from 30 hyperprolinemic subjects bore at least one genetic variation associated with hyperprolinemia. This study demonstrates that moderate hyperprolinemia is an intermediate phenotype associated with certain forms of psychosis.

Abnormal sensory gating in schizophrenia has frequently been reported. The strength of central inhibitory pathways was measured using the P50 component of the auditory evoked potential in a conditioning–testing paradigm. The relationships between a relative decrease in P50 amplitude to repeated auditory stimuli and clinical symptoms remain controversial. Using the Positive and Negative Syndrome Scale, we studied the P50 auditory conditioning–testing paradigm in 81 schizophrenic subjects, categorized into subgroups with and without prominent negative symptoms, in comparison with 88 control subjects. We found increased ratios of testing stimuli to conditioning stimuli in both schizophrenic subgroups relative to findings in the control group. In addition, we found significantly increased mean latencies of the P50 responses to conditioning (C) and testing (T) stimuli and significantly increased T/C ratios in the subgroup with negative symptoms compared with the subgroup with non-negative symptoms.

Angular distributions of recoiling He2+ and He+ ions following collisions of slow O5+ ions and He atoms were measured, for projectile energies in the range 100-2500 eV. The recoil ions were detected at angles from 20degrees to 130degrees. Two groups of peaks are clearly visible, corresponding to single and double electron capture. Highly energetic He2+ and He+ ions were observed at forward angles. It has already been shown in previous works on the C5+ and B5+ + He collisions that recoiling He+ targets mainly originate from a single electron capture on the n = 2 or 3 orbitals of the projectile, whereas He2+ ions are due to a double electron capture on 2lnl'(n > 2) configurations. The population of such configurations is confirmed by our model calculations based on classical kinematics equations. From this model, charge exchange probabilities P(b), where b is the impact parameter, were deduced for the explored projectile energies. To explain the large kinetic energies for recoil targets, we had to invoke electron capture processes under small impact parameter conditions (b < 1 au). At 2500 eV, while the capture events occurring at large impact parameters are not detected in the present measurements, electron capture in collisions at small impact parameters is evidenced. At the lowest projectile energy (100 eV) we have access to the whole range of impact parameters. The contribution of small impact parameters is shown to be dominant at this energy.

As suggested by several studies, abnormal sensory gating measured by the P50 paradigm could be an endophenotype predisposing to schizophrenia. In a previous work, we have shown a significant association between the presence of at least one −2 bp deletion located within exon 6 of the CHRNA7- like gene and the P50 abnormality in the general population. A recent study involved polymorphisms located in the core promoter region of the CHRNA7 gene as risk factors for the P50 inhibitory deficit. Screening for promoter variants in a large population of schizophrenic patients ( n =111) and control subjects (85), for whom auditory-evoked potentials had been recorded did not allow us to replicate these results. By contrast, we showed a significant association between the −194 C allele and a T/C ratio <0.45, thus demonstrating a protective effect of this variant for the sensory gating deficit. Such conflicting results can be reconciled if we consider that the −194 C polymorphism has no causative effect, but is in linkage disequilibrium with other causal variations for the P50 sensory gating deficit, and that different alleles are in disequilibrium in different populations.

Abnormality in the P50 auditory-evoked potential gating is an endophenotype associated with schizophrenia. Biochemical and genetic studies have suggested that the alpha 7 nicotinic acetylcholine receptor (nAChR) is involved in this sensory gating deficit. Two related alpha 7 genes (CHRNA7 and CHRNA7-like gene) resulting from a partial duplication (from exon 5 to exon 10) are present in the human genome. Two types of genetic variation, a large deletion and a −2 base-pair deletion in exon 6 resulting in a truncation of the open reading frame, affect specifically the CHRNA7-like gene. We developed a simple multiplex PCR assay on genomic DNA, allowing the quantification of the number of exons 6 and the distinction of all possible exon 6 genotypes. Genotyping of 70 schizophrenic patients and 77 controls showed that carrying at least one −2 bp deletion of exon 6 did not constitute a risk factor for schizophrenia. In contrast, the distribution of genotypes differed significantly between subjects with normal and abnormal P50 ratios, with an over-representation of genotypes carrying at least one −2 bp deletion of exon 6 among subjects exhibiting an abnormal P50 ratio. We thus conclude that the −2 bp deletion within the CHRNA7-like gene is a risk factor for P50 sensory gating deficit. Interestingly, most of the effect came from the non schizophrenic group, which may suggest that in schizophrenic patients other risk factors account for the large proportion of subjects exhibiting an abnormal P50 ratio.

The increased prevalence of schizophrenia among patients with the 22q11 interstitial deletion associated with DiGeorge syndrome has suggested the existence of a susceptibility gene for schizophrenia within the DiGeorge syndrome chromosomal region (DGCR) on 22q11. Screening for genomic rearrangements of 23 genes within or at the boundaries of the DGCR in 63 unrelated schizophrenic patients and 68 unaffected controls, using quantitative multiplex PCR of short fluorescent fragments (QMPSF), led us to identify, in a family including two schizophrenic subjects, a heterozygous deletion of the entire PRODH gene encoding proline dehydrogenase. This deletion was associated with hyperprolinemia in the schizophrenic patients. In addition, two heterozygous PRODH missense mutations (L441P and L289M), detected in 3 of 63 schizophrenic patients but in none among 68 controls, were also associated with increased plasma proline levels. Segregation analysis within the two families harboring respectively the PRODH deletion and the L441P mutation showed that the presence of a second PRODH nucleotide variation resulted in higher levels of prolinemia. In two unrelated patients suffering from severe type I hyperprolinemia with neurological manifestations, we identified a homozygous L441P PRODH mutation, associated with a heterozygous R453C substitution in one patient. These observations demonstrate that type I hyperprolinemia is present in a subset of schizophrenic patients, and suggest that the genetic determinism of type I hyperprolinemia is complex, the severity of hyperprolinemia depending on the nature and number of hits affecting the PRODH locus.