Age at the time of onset of psychosis: A marker of specific needs rather than a determinant of outcome?

BACKGROUND: While there is suggestion that early onset of psychosis is a determinant of outcome; knowledge regarding correlates of later onset age is more limited. This study explores the characteristics of patients developing psychosis after age 26, towards the end of the usual age range of early intervention programs, in order to identify potential specific needs of such patients. METHODS: Two hundred and fifty-six early psychosis patients aged 18-35 were followed-up prospectively over 36 months. Patients with onset after 26 ("later onset", LO) were compared to the rest of the sample. RESULTS: LO patients (32% of the sample) had shorter DUP, were less likely to be male, had better premorbid functioning and were more likely to have been exposed to trauma. They had greater insight at presentation and less negative symptoms overall. The trajectories for positive and depressive symptoms were similar in both groups. Evolution of functional level was similar in both groups, but while LO patients recovered faster, they were significantly less likely to return to premorbid functional level. CONCLUSIONS: Later psychosis onset correlates with better premorbid functioning and higher rate of trauma exposure; the latter should therefore be a treatment focus in such patients. LO patients were less likely to return to premorbid functional level, which suggests that current treatment strategies may not be efficient to help patients maintain employment. The possibility of distinct illness mechanisms according to onset age and the more central role for trauma in patients with onset after age 26 needs to be further explored.

[From early treatment of psychosis risk to the risks of early intervention: the dilemma of psychosis prevention]. / Du traitement précoce des sujets à risque aux risques du traitement précoce. Le dilemme de la prévention des troubles psychotiques.

While the development of early psychosis intervention programs have improved outcome of such disorders, primary prevention strategies are still out of reach. The elaboration, over the last 15 years, of scales and criteria to identify populations at high risk for psychosis is a real progress, but their low specificity is still a major obstacle to their use outside of research projects. For this reason, even if "ultra high risk", subjects present with real psychiatric disorders and sometimes significant decrease in functioning level, the fact that only a small proportion will eventually develop full blown psychosis will probably lead to the rejection of a "psychosis risk syndrom" from the future DSM-V classification.

[Follow-up of the metabolic syndrome induced by atypical antipsychotics: recommendations and pharmacogenetics perspectives]. / Suivi du syndrome métabolique induit par les antipsychotiques atypiques: recommandations et perspectives pharmacogénétiques.

Despite a better overall tolerance as compared to classical antipsychotics, atypical antipsychotics are not devoid of side-effects, notably metabolic factors (weight gain, alteration of lipid and glucose profile). These side-effects are very troubling concerning long term morbidity and mortality and may also influence compliance towards drugs. The department of psychiatry of the Hospital University Centre has established a guideline on the clinical monitoring of patients receiving atypical antipsychotics, based on recently published consensus, which will be presented here. In addition, recent studies show that weight gain and metabolic alterations induced by this type of medication may be influenced by the genetic background of the patients. Such studies should allow, in the near future, to adapt the treatment for each patient.

Autosomal dominant dopa-responsive parkinsonism in a multigenerational Swiss family.

AIM: To describe a large family with autosomal dominant parkinsonism. BACKGROUND: Seven genes are directly implicated in autosomally inherited parkinsonism. However, there are several multigenerational large families known with no identifiable mutation. MATERIAL AND METHODS: Family members were evaluated clinically, by history and chart review. Genetic investigation included SCA2, SCA3, UCHL1, SNCA, LRRK2, PINK1, PRKN, PGRN, FMR1 premutation, and MAPT. The proband underwent brain fluorodopa PET (FD-PET) scan, and one autopsy was available. RESULTS: Eleven patients had a diagnosis of Parkinson's disease (PD), nine women. Mean age of onset was 52 with tremor-predominant dopa-responsive parkinsonism. Disease progression was slow but severe motor fluctuations occurred. One patient required subthalamic nucleus deep-brain stimulation with a good motor outcome. One patient had mental retardation, schizophrenia and became demented, and another patient was demented. Three patients and also two unaffected subjects had mild learning difficulties. All genetic tests yielded negative results. FD-PET showed marked asymmetric striatal tracer uptake deficiency, consistent with PD. Pathological examination demonstrated no Lewy bodies and immunostaining was negative for alpha-synuclein. CONCLUSION: Apart from a younger age of onset and a female predominance, the phenotype was indistinguishable from sporadic tremor-predominant PD, including FD-PET scan results. As known genetic causes of autosomal dominant PD were excluded, this family harbors a novel genetic defect.

Study of a Swiss dopa-responsive dystonia family with a deletion in GCH1: redefining DYT14 as DYT5.

OBJECTIVE: To report the study of a multigenerational Swiss family with dopa-responsive dystonia (DRD). METHODS: Clinical investigation was made of available family members, including historical and chart reviews. Subject examinations were video recorded. Genetic analysis included a genome-wide linkage study with microsatellite markers (STR), GTP cyclohydrolase I (GCH1) gene sequencing, and dosage analysis. RESULTS: We evaluated 32 individuals, of whom 6 were clinically diagnosed with DRD, with childhood-onset progressive foot dystonia, later generalizing, followed by parkinsonism in the two older patients. The response to levodopa was very good. Two additional patients had late onset dopa-responsive parkinsonism. Three other subjects had DRD symptoms on historical grounds. We found suggestive linkage to the previously reported DYT14 locus, which excluded GCH1. However, further study with more stringent criteria for disease status attribution showed linkage to a larger region, which included GCH1. No mutation was found in GCH1 by gene sequencing but dosage methods identified a novel heterozygous deletion of exons 3 to 6 of GCH1. The mutation was found in seven subjects. One of the patients with dystonia represented a phenocopy. CONCLUSIONS: This study rules out the previously reported DYT14 locus as a cause of disease, as a novel multiexonic deletion was identified in GCH1. This work highlights the necessity of an accurate clinical diagnosis in linkage studies as well as the need for appropriate allele frequencies, penetrance, and phenocopy estimates. Comprehensive sequencing and dosage analysis of known genes is recommended prior to genome-wide linkage analysis.

Cerebellum and procedural learning: evidence from focal cerebellar lesions.

The aim of the present study was to investigate the influence of focal cerebellar lesions on procedural learning. Eight patients with cerebellar lesions and six control subjects were tested in a serial reaction-time task. A four-choice reaction-time task was employed in which the stimuli followed (or not) a sequence repeated 10 times, with the subjects aware (or not) of the item sequence. Learning was manifested by the reduction in response latency over the sequential blocks. Acquisition of declarative knowledge of the sequence was also tested. Reaction times displayed by patients with cerebellar lesions, even though they tended to be longer than those of control subjects in all testing conditions, significantly differed from control subjects only when the stimuli were presented in sequence. The reaction times in sequential trials were still statistically significant when simple motor response times were taken into account. Cerebellar patients were also significantly impaired in detecting and repeating the sequence. On the other hand, when the sequence was learned before testing, motor performances were significantly improved in all subjects. These data indicate that cerebellar lesions induce specific impairment in the procedural learning of a motor sequence and suggest a role of the cerebellar circuitry in detecting and recognizing event sequences.

Cognitive impairment in asymptomatic stages of HIV infection. A longitudinal study.

Seventy-eight asymptomatic HIV-seropositive (aHIV) subjects were examined by means of an extensive neuropsychological test battery in comparison with 32 HIV-seronegative controls. They were also tested with regard to CD4+ and serum p24 antigen. Fifty-six of them completed a clinical follow-up of 12 up to 36 months and 35 also underwent a second session of neuropsychological, CD4+ and p24 antigen assessments at a 12- to 18-month interval from the first session. Results obtained lead to the following conclusions: (a) even among aHIV subjects there is a significant prevalence (28.2%) of cognitive abnormalities for which no cause other than HIV can be found, and therefore this suggests the possible development of HIV-related brain damage since the earliest stages of infection; (b) most sensitive to early HIV-related cognitive impairment are timed psychomotor tasks and memory tasks which require attention, learning and 'active' monitoring or retrieval of information; (c) during the early asymptomatic stages of HIV infection, there is no clear-cut evidence of a cross-sectional relationship between cognition and immunological/ virological markers (at least in the high ranges of CD4+ cell counts considered here); only in relatively more advanced stages does this relationship become evident in the subgroup of aHIV subjects with cognitive abnormalities; (d) the presence of cognitive abnormalities in early HIV infection is predictive of a further decrease in cognitive functioning and faster progression to AIDS-this latter reflected by a faster rate of decline in the number of CD4+ cells and by an increase in positivity of serum p24 antigen.