Pierre Lalonde

Cognitive predictors of psychosocial functioning outcome in schizophrenia: A follow-up study of subjects participating in a rehabilitation program

The aims of this prospective study were to explore in subjects with psychosis participating in a rehabilitation program whether cognitive performances at baseline predicted (i) psychosocial functioning over a 15-16 month follow-up; (ii) improvement in psychosocial functioning over the rehabilitation program. Visuo-spatial tests from the Cambridge Neuropsychological Test Automated Battery (CANTAB) were administered to assess cognitive performance in 55 subjects with schizophrenia spectrum disorders who completed a rehabilitation program. The Multnomah Community Ability Scale (MCAS) was used to measure dimensions of community functioning. One subscale of the Clients Assessment of Strengths, Interests, and Goals (CASIG) provided a measure of subjective quality of life (QoL). Improvement was defined as a 15% or more increase in psychosocial scores between baseline and follow-up. Worse baseline sustained attention predicted better self-rated quality of life, and better baseline visual memory predicted better community functioning over the rehabilitation follow-up period, in particular, higher autonomy in activities of daily living, and less physical and psychiatric symptoms that could interfere with rehabilitation. Baseline cognitive performances predicted community functioning improvement during the follow-up period: visual memory predicted improvement in daily living autonomy and in social competence; sustained attention predicted improvement in behavioral problems (such as medication compliance, collaboration with treatment providers or impulse control) and social competence; planning performances predicted improvement in social competence. These cognitive functions could be specifically targeted in a rehabilitation program aimed at enhancing functioning in those particular dimensions.

Self-assessed cognitive dysfunction and objective performance in outpatients with schizophrenia participating in a rehabilitation program

OBJECTIVE To explore the pattern of associations between self-assessed and objective neuropsychological performance in a sample of outpatients with schizophrenia participating in a rehabilitation program. METHOD The Subjective Scale to Investigate Cognition in Schizophrenia (SSTICS) [Compr. Psychiatry 44 (2003) 331] was used to assess cognitive complaints in 73 subjects with schizophrenia. Visuo-spatial tests of the Cambridge Neuropsychological Test Automated Battery (CANTAB) [Cogn. Neuropsychiatry 3 (1998) 45] were administered as objective measures. RESULTS Cognitive complaints in several cognitive domains were mainly correlated with a true difficulty in memory. Higher SSTICS attention scores, i.e. increased complaints, were associated with poorer CANTAB explicit visual memory and planning performances. Higher SSTICS executive functioning scores were associated with poorer CANTAB explicit visual memory scores. CONCLUSION These findings suggest that outpatients with schizophrenia express some cognitive difficulties. However, the cognitive nature of these subjective complaints does not strictly correspond with objective performances. These results also suggest that theoretical constructs of cognitive functions do not always have ecological validity. Thus, subjective cognitive complaints should be taken into account in assessment of patient well-being, but cannot be used as a substitute to objective cognitive measures. The simultaneous use of subjective and objective measures of cognitive dysfunction may provide a more complete picture of individual rehabilitation targets in patients with schizophrenia.

Cognitive discernible factors between schizophrenia and schizoaffective disorder

BACKGROUND Schizophrenia (SZ) and schizoaffective disorders (SA) are associated with cognitive deficits. Generally, a schizoaffective diagnosis is associated with better prognosis on the level of social integration. It is also well established that cognition is an important factor for good social outcome in schizophrenia. We hypothesized that, although patients suffering from SA share symptoms with SZ, they can be differentiated on the basis of neurocognitive function and that SA perform better in several domains. METHOD Performances of two groups SA (N = 13) and SZ (N = 44) were compared on several visual-motor tasks using CANTAB [Motor Screening (MOT), Reaction Time (RTI), Paired Associates Learning Task (PAL), and Stockings of Cambridge items (SOC)]. The two groups were matched for symptom severity. ANOVA with repeated measures was employed to determine whether any difference in cognitive scores during a 2-year period was significantly related to the diagnostic status. RESULTS A significant and durable difference was observed between SZ and SA on motor screening and explicit memory tests where SA performed better. CONCLUSION Neurocognitive tests may be relevant for distinguishing schizoaffective from schizophrenia, chiefly via tests tapping into visuo-spatial and visuo-motor coordination abilities (e.g., paired associated learning and motor screening).

CANTAB explicit memory is less impaired in addicted schizophrenia patients

It has been suggested that in order to sustain the lifestyle of substance abuse, addicted schizophrenia patients would have less negative symptoms, better social skills, and less cognitive impairments. Mounting evidence supports the first two assumptions, but data lack regarding cognition in dual diagnosis schizophrenia. Seventy-six schizophrenia outpatients (DSM-IV) were divided into two groups: with (n = 44) and without (n = 32) a substance use disorder. Motor speed and visuo-spatial explicit memory were investigated using CANTAB. As expected, dual diagnosis patients showed a better cognitive performance. Our results suggest either that substance abuse relieves the cognitive deficits of schizophrenia or that the patients with less cognitive deficits are more prone to substance abuse.

Benefits and risks of antipsychotic polypharmacy: an evidence-based review of the literature.

Combination antipsychotic prescription is an increasingly common practice in clinical psychiatry. This clinical practice is at odds with clinical guidelines promoting antipsychotic monotherapy. Moreover, there has been increased concern over the safety profile of atypical antipsychotics in the last 10–15 years. We reviewed the literature on antipsychotic combinations with a focus on safety and efficacy. Multiple electronic database searches were complemented by relevant bibliography cross-checking and expert discussions. The review showed a literature that is dominated by case reports and uncontrolled studies. Polypharmacy was unequally studied, with some recent combinations (i.e. clozapine and risperidone) being extensively, albeit inconclusively, studied and other more commonly used combinations (first-with second-generation agents) receiving little attention. From an evidence-based perspective, further trials of antipsychotic association of sufficient power to address safety issues are needed before recommending any antipsychotic combination. Particular weaknesses of the present literature are low number of participants, lack of adequate control of confounding variables, short duration of experimental follow-up and inadequate monitoring of potential adverse effects.

DRD3 and DAT1 genes in schizophrenia: an association study.

OBJECTIVE To investigate the role of the dopamine receptor 3 (DRD3) and transporter 1 (DAT1) genes in schizophrenia or in modulating its phenotype. METHODS a Ser9Gly polymorphism in codon 9 of the DRD3 and a VNTR polymorphism in the DAT1genes were examined in two groups of schizophrenic patients, one of excellent neuroleptic responders (N=42) and one of nonresponders (N=64). A group of healthy volunteers screened for major psychiatric disorders was also included (N=89). In addition, age at onset of psychotic symptoms, attention performance and family loading for schizophrenia spectrum disorders were compared between patients with different genotypes in the DRD3 and DAT1 genes. RESULTS No significant differences in the allelic distribution of the DRD3 and DAT1 polymorphisms were detected between schizophrenic patients and controls. A trend toward an excess of DRD3 genotype Gly/Gly was observed in neuroleptic nonresponder schizophrenic patients compared to controls (chi(2)=3. 30, df=1, p=0.07). No significant differences in age at onset of psychotic symptoms, attention task performance or family loading for schizophrenia spectrum disorders were observed between groups with different DRD3 and DAT1 genotypes. CONCLUSION These results do not support the role of either of these genes in increasing susceptibility to schizophrenia or in modulating its phenotype in the studied population.

Neuropsychological impairments in neuroleptic-responder vs. -nonresponder schizophrenic patients and healthy volunteers.

To determine whether two groups of schizophrenic patients representing the two extremes of the neuroleptic response-spectrum (consistent responders vs. consistent nonresponders) differ with respect to their neuropsychological profile. Neuroleptic-responder (R; n=36) and -nonresponder (NR; n=39) schizophrenic patients were recruited according to a priori defined criteria of responsiveness to typical neuroleptics. Seven neuropsychological domains were assessed and compared between groups: attention-vigilance, abstraction-flexibility, spatial organization, visual-motor processing, visual memory, verbal abilities, and verbal memory and learning. All measures were standardized using the scores of 36 healthy volunteers. NR schizophrenic patients performed worse in all neuropsychological domains compared to normal controls and R schizophrenic patients. However, only performances on visual memory, verbal abilities, and verbal memory and learning were significantly poorer in NR compared to R patients. Only the latter domain significantly differentiated NR patients from the other two groups. R patients performed at an intermediate level in all domains. This report of differences in neuropsychological profile between neuroleptic-responder and -nonresponder schizophrenic patients adds to the growing evidence supporting the value of distinguishing schizophrenic patients on the basis of their therapeutic response to neuroleptics.

Analysis of 14 CAG repeat-containing genes in schizophrenia.

Recently, it has been suggested that trinucleotide repeat-containing genes may be involved in the etiology of schizophrenia. This study was aimed at investigating putative associations between allelic variants or expansions of CAG repeat-containing genes (CAGrCG) and schizophrenia or its variability with respect to responsiveness to conventional neuroleptics. CAG repeat allelic variants of 14 expressed sequences were compared among three groups of subjects: neuroleptic-responder (R; n = 43) and neuroleptic-nonresponder (NR; n = 63) schizophrenic patients, and a control group (C; n = 122). No CAG expansions, in the range of those observed in neurodegenerative diseases, were identified in these 14 expressed sequences. The sizes of CAG repeat for the hGT1 gene were marginally different among the three groups of subjects (Kruskal-Wallis H (2, 456) = 10.48, Bonferroni corrected P = 0.047). Comparisons among the different groups indicated that neuroleptic responders have shorter alleles compared to controls (Mann-Whitney adjusted Z = -3.23, P = 0.0012). NR patients were not different from controls. These preliminary results suggest that the hGT1 gene, or a gene in its vicinity, may be involved in the etiology of schizophrenia or in modifying the disease phenotype with regard to outcome and/or neuroleptic responsiveness. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 88:694-699, 1999.

Dopamine Beta-Hydroxylase (DBH) gene and schizophrenia phenotypic variability: A genetic association study

Recently, two polymorphisms (DBH5′‐Ins/del and DBH 444 g/a) of the Dopamine Beta Hydroxylase (DBH) gene were isolated, and one haplotype (Del‐a) was found to be associated with low DBH activity and cocaine‐induced paranoia. The purpose of this study is to test for association between these two polymorphisms and schizophrenia or its phenotypic variability with respect to neuroleptic therapeutic response and symptom profile. Allelic and haplotype distributions of these two polymorphisms were compared between two groups of schizophrenic patients (excellent neuroleptic‐responders; R, n = 42 and non‐responders; NR, n = 64), and one group of healthy volunteers (n = 120). The “Del” and “a” alleles were in positive linkage disequilibrium. No allelic or genotype differences in the distribution of these two polymorphisms were observed between patients and controls. However, The Del‐a haplotype was significantly more common in NR patients, and the mean total BPRS score was significantly higher in the group of patients with the Del‐a compared to those without the Del‐a haplotype. These results suggest that the DBH gene is not a causative factor in schizophrenia but that it may be a modulator of psychotic symptoms, severity of the disorder and therapeutic response to neuroleptic drugs.

The cognitive and anatomo-functional basis of reality distortion in schizophrenia: A view from memory event-related potentials

This study investigated the neural and cognitive correlates of reality distortion in schizophrenia by using event-related potentials (ERPs) recorded in a recognition memory task for face. This task has been chosen because previous studies have shown that it provides distinct indices related to specific cognitive processes and to the functioning of specific brain regions. ERPs have been recorded in controls and schizophrenia patients separated into high scorers (RD+) and low-scorers (RD-) according to their Reality Distortion score (hallucination and delusion SAPS subscales). The results indicate that RD+ presents abnormalities on various cognitive processes. First, RD+ are deficient at interference inhibition and knowledge integration (reduced P2a and N400 effect). The similar impairments found in RD- suggest that they represent basic traits of the illness. Second, RD+ showed inappropriate stimulus categorization and contextual integration (larger N300 and fronto-central effect). Third, RD+ showed a late index (P600 effect) not different from controls, but larger than in RD-. This result is consistent with a qualitative, rather than quantitative, impairment of mnemonic binding processes (inappropriate binding) in RD+. Since each of the ERP abnormalities observed represents associated with distinct brain dysfunction, the results are further discussed in regard of the respective contribution of the parietal, frontal and hippocampal structures to reality distortion symptoms.