Empirical validity of Leonhard's psychoses: A long-term follow-up study of first-episode psychosis patients.

The validation of nosological diagnoses in psychiatry remains a conundrum. Leonhard's (1979) nosology seems to be one of the few acceptable alternative categorical models to current DSM/ICD systems. We aimed to empirically validate Leonhard's four classes of psychoses: systematic schizophrenia (SSch), unsystematic (USch), cycloid psychosis (Cyclo), and manic-depressive illness (MDI) using a comprehensive set of explanatory validators. 243 patients with first-episode psychosis were followed between 10 and 31 years. A wide-ranging assessment was carried out by collecting data on antecedent, illness-related, concurrent, response to treatment, neuromotor abnormalities, and cognitive impairment variables. Compared with USch, Cyclo, and MDI, SSch displayed a pattern of impairments significantly larger across the seven blocks of explanatory variables. There were no significant differences between Cyclo and MDI in explanatory variables. Except for the majority of illness-onset features, USch displayed more substantial abnormalities in the explanatory variables than Cyclo and MDI. SSch and MDI showed higher percentages of correctly classified patients than USch and Cyclo in linear discriminant analyses. Partial validation of Leonhard's classification was found. SSch showed differences in explanatory variables with respect to Cyclo and MDI. USch showed also significant differences in explanatory variables regarding Cyclo and MDI, although with a lower strength than SSch. There was strong empirical evidence of the separation between both Leonhard's schizophrenia subtypes; however, the distinction between the Cyclo and MDI groups was not empirically supported. A mild to moderate discriminative ability between Leonhard's subtypes on the basis of explanatory blocks of variables was observed.

Effect of polygenic risk score, family load of schizophrenia and exposome risk score, and their interactions, on the long-term outcome of first-episode psychosis.

BACKGROUND: Consistent evidence supports the involvement of genetic and environmental factors, and their interactions, in the etiology of psychosis. First-episode psychosis (FEP) comprises a group of disorders that show great clinical and long-term outcome heterogeneity, and the extent to which genetic, familial and environmental factors account for predicting the long-term outcome in FEP patients remains scarcely known. METHODS: The SEGPEPs is an inception cohort study of 243 first-admission patients with FEP who were followed-up for a mean of 20.9 years. FEP patients were thoroughly evaluated by standardized instruments, with 164 patients providing DNA. Aggregate scores estimated in large populations for polygenic risk score (PRS-Sz), exposome risk score (ERS-Sz) and familial load score for schizophrenia (FLS-Sz) were ascertained. Long-term functioning was assessed by means of the Social and Occupational Functioning Assessment Scale (SOFAS). The relative excess risk due to interaction (RERI) was used as a standard method to estimate the effect of interaction of risk factors. RESULTS: Our results showed that a high FLS-Sz gave greater explanatory capacity for long-term outcome, followed by the ERS-Sz and then the PRS-Sz. The PRS-Sz did not discriminate significantly between recovered and non-recovered FEP patients in the long term. No significant interaction between the PRS-Sz, ERS-Sz or FLS-Sz regarding the long-term functioning of FEP patients was found. CONCLUSIONS: Our results support an additive model of familial antecedents of schizophrenia, environmental risk factors and polygenic risk factors as contributors to a poor long-term functional outcome for FEP patients.

Neurocognitive correlates of the varied domains of outcomes at 20 year follow-up of first-episode psychosis.

Little is known about long-term outcomes of the first episode of psychosis (FEP) other than in the symptomatic domain. We hypothesised that cognitive impairment is associated with poorer multi-domain outcomes at a long-term follow-up of FEP patients. We followed-up 172 FEP patients for a mean of 20.3 years. Ten outcome dimensions were assessed (symptomatic, functional and personal recovery, social disadvantage, physical health, suicide attempts, number of episodes, current drug use, chlorpromazine equivalent doses (CPZ), and schizophrenia/schizoaffective disorder final diagnosis). Cognition was assessed at follow-up. Processing speed and verbal memory deficits showed significant associations with poor outcomes on symptomatic, social functioning, social disadvantage, higher number of episodes, and higher CPZ. Significant associations were found between visual memory impairments were significantly associated with low symptomatic and functional recovery, between attentional deficits and a final diagnosis of schizophrenia/schizoaffective disorder, and between social cognition deficits and poor personal recovery.Lower cognitive global scores were significantly associated with all outcome dimensions except for drug abuse and physical status. Using multiple outcome dimensions allowed for the inclusion of the patients' perspective and other commonly neglected outcome measures. Taken together, cognitive impairment in FEP patients is strongly related to poor performance on several outcome dimensions beyond symptomatic remission.

The woodchuck hepatitis virus post-transcriptional regulatory element reduces readthrough transcription from retroviral vectors.

The woodchuck hepatitis virus post-transcriptional regulatory element (WPRE) increases transgene expression from a variety of viral vectors, although the precise mechanism is not known. WPRE is most effective when placed downstream of the transgene, proximal to the polyadenylation signal. We hypothesized that WPRE likely reduces viral mRNA readthrough transcription by improving transcript termination, which in turn would increase viral titers and expression. Using a Cre-lox-mediated plasmid-based assay, we found significant readthrough transcription from gamma-retroviral vector (RV) long terminal repeat (wt RV-LTR) and RV LTR with a self-inactivating deletion (SIN RV-LTR). WPRE, when placed upstream of the RV LTRs, significantly reduced readthrough transcription. Readthrough, present at much lower levels with the SIN HIV-1 LV-LTR, was also reduced with WPRE. When placed in RV vectors, WPRE increased total RV genomic mRNA; and increased viral titers from transiently transfected 293T cells and stable PG13 producer cells by 7- to 15-fold. The mechanism of increased titers and expression was not due to increased nuclear mRNA export, increased rate of viral transcription or a significant increase in viral mRNA half-life. Our results showed that WPRE improved vector genomic transcript termination to increase titers and expression from RVs.

[Psychological factors and psychotherapeutic approaches in depressive disorders]. / Factores psicológicos y abordajes psicoterapéuticos de los trastornos depresivos.

This paper reviews the contributions of the different psychological orientations to the understanding and treatment of depressive disorders. Special emphasis is placed on explaining the foundations and methodology of the psychotherapeutic alternatives that at present enjoy the widest diffusion. Finally, reflection on the complexity of the depressive pictures, and on the reality within which the person suffering from this disorder is immersed, obliges us to support the recommendation of combined therapies, to emphasise the lack of a solid body of research concerning the efficacy of the treatments and the adjustment of the different modalities of psychotherapy to the different disorders and depressive patients, and to recommend that preventive strategies should be taken into account as well as those of treatment.

Are personality traits associated with cognitive disturbance in psychosis?

OBJECTIVE: Personality and cognition are often considered as disparate constructs, both in normal individuals and in those with a psychosis. The goal of the present study was to analyze the relationship between dimensions of personality and cognitive performance in individuals with psychosis. METHODS: Sixty-one consecutively admitted patients with an acute psychotic episode were recruited for this study. Personality was assessed through a semistructured interview with a close relative using the Personality Assessment Schedule. A wide neuropsychological battery was applied, including attentional, executive, memory tasks and global cognition. Assessments took place when symptomatology was in remission. RESULTS: Higher scores on a passive-dependent dimension were significantly associated with poorer memory performance. Similarly, higher levels for a schizoid dimension were significantly associated with poorer executive performance. The results remained significant after partialling out the effect of gender, psychopathological dimensions and drug status. CONCLUSION: It is hypothesized that personality traits and cognitive performance are interrelated domains in psychosis.

Effects of olanzapine and other antipsychotics on cognitive function in chronic schizophrenia: a longitudinal study.

This study aimed to determine the effect of olanzapine and other antipsychotic drugs on cognitive functions after 6months of treatment. Baseline, 3month and 6month psychopathological and cognitive evaluations were made. Thirty-eight partially responsive outpatients with DSM-IV chronic schizophrenia diagnosis were included in the study. On the indication of their attending psychiatrists, 21 patients initiated treatment with olanzapine, and 17 remained on their previous treatment with other antipsychotic drugs. Cognitive assessments were blind to medication and psychopathological status. The olanzapine group presented a significantly greater improvement in negative symptomatology and verbal memory than the comparison group in repeated-measures of MANOVAs between baseline, 3month and 6month assessments. These differences remained statistically significant after covarying out gender, treatment with other atypical antipsychotics, biperidene doses and changes in positive and negative symptoms. In order to match previous differences between groups, cognitive baseline scores for each test were introduced as covariates, resulting in a significant improvement for the olanzapine group in negative symptomatology and the interference task of the Stroop test.We then re-analyzed the data, dividing the comparison group into two groups: risperidone-treated patients (n=9) and patients receiving conventional antipsychotic drugs (n=8). Post-hoc analyses between groups were carried out with baseline cognitive assessment as covariate. The olanzapine group improved significantly more than the risperidone group in negative symptomatology and in the interference task of Stroop test. The improvement in the number of categories of the Wisconsin Card Sorting Test was higher in risperidone patients than in those receiving olanzapine or conventional antipsychotic treatment. Conventional antipsychotic drugs did not present a significant improvement over atypical antipsychotic drugs in any cognitive function. In summary, in patients suffering from chronic schizophrenia, atypical antipsychotic agents were associated with slight differential improvements over time in attentional, verbal memory and executive functions compared with conventional neuroleptic drugs. No differential improvements were found in social functioning, verbal fluency, non-verbal domains of memory or visuo-motor abilities.

Reappraising insight in psychosis. Multi-scale longitudinal study.

BACKGROUND: Many patients suffering from psychosis are unaware of their disorder and symptoms. AIMS: To investigate whether insight changes with time, and how it relates to patients' psychopathology, and to examine the correlations between insight scales in patients with psychoses. METHODS: Seventy-five consecutively admitted in-patients with schizophrenia, affective disorder with psychotic symptoms, or schizoaffective disorder were examined after remission of an acute episode and at follow-up (> 6 months). Three different scales were used to assess insight. RESULTS: To some extent, insight into past episodes improved over time in patients with psychosis, regardless of diagnosis. Few significant relationships between insight and psychopathology remained stable at follow-up. The higher the negative and disorganisation dimensions at baseline, the less did attitudes to treatment vary when tested at follow-up. No predictive value for variability of psychopathological dimensions was found for insight dimensions. The insight scales used were highly intercorrelated, suggesting that they measure the same construct. CONCLUSIONS: Insight and psychopathology seem to be semi-independent domains.

Illness duration and neuropsychological impairments in schizophrenia.

This study aims to verify whether cognitive disturbances in schizophrenic patients are associated with illness duration, and to examine the influence of other covariates on neuropsychological disturbances. Sixty-nine consecutive admissions of schizophrenic patients (DSM-III-R, APA, 1987) were included to an acute psychiatric unit. Patients were evaluated by a semistructured interview and assessed with the Scale for the Assessment of Positive Symptoms (SAPS) and the Scale for the Assessment of Negative Symptoms (SANS). A wide neuropsychological battery, adapted to Spanish, was used. Variables were transformed to z-scores when their distribution was normal, or to log-values in the case of non-normal distributions. Pearson's correlation coefficients with a Bonferroni correction showed strong relationships between illness duration and cognitive performance in neuropsychological tests on visuomotor processes and delayed visual memory. In order to examine the influence of potential covariates on neuropsychological disturbances, stepwise multiple regression procedures were performed with each neuropsychological measure as a dependent variable, and years of education, age, gender, neuroleptic does in chlorpromazine equivalents, biperidene doses and illness duration as independent variables. The longer the illness duration, the poorer the performance on visuomotor process and delayed visual memory tasks. Moreover, the neuropsychological disturbances associated with illness duration were different from those related to aging, educational background, gender and treatment status. These findings suggest the existence of a relationship between cognitive decline in visuomotor and delayed visual memory functions and the length of schizophrenic illness.

Psychopathological dimensions and lack of insight in schizophrenia.

The present study investigated the relationships of psychopathological dimensions of schizophrenia with Insight in a sample of 100 acute schizophrenic patients. Lack of insight was significantly correlated with disorganized, excited and negative schizophrenic dimensions but not with other Positive and Negative Syndrome Scale dimensions. In addition, when insight was assessed through a multidimensional approach, a variety of relationships with the schizophrenic dimensions were found.